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Studies Linking Prostate Cancer and PCBs
The following 22 studies show the possibility that PCBs contribute to
prostate
cancer risks. This is not a complete list of all studies on this
topic. For more, visit the TOXNET
database operated by the National Library of Medicine (the source of these
abstracts). Keep in mind that these studies are not all equal in
size or quality. Some were published in peer-reviewed journals, while
others were simply presented at conferences. A few are duplicates
by the same author (one conference-based, another published) but we presented
both because the descriptions were slightly different.
Go to: Summary
of Results
Study #1
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PCBs increased prostate size at a dosage consumed by the general public
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permanently increased androgen receptor (AR) binding activity of the prostate
at a dosage consumed by the general public
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induced prostate growth in the presence and absence of testosterone; however,
it was more effective in the presence of testosterone
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estrogenic chemicals [such as PCBs] induce reproductive malformation by
direct interference with the fetal reproductive organs
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PCBs are able to induce malformation even in the absence of fetal testosterone;
however, they are more effective in the presence of testosterone
Recently, significant concerns have been placed on the widespread use of
chemicals with persistent estrogenic activity for their long-term effects
on human health. In this communication, we investigated whether fetal exposure
to some of these chemicals at doses consumed by people, has any long-term
effect on the reproductive functions of the male offspring. Thus, time-pregnant
CD-1 mice were fed diethylstilbestrol (DES), bisphenol A (BPA), and Aroclor
(Aroclor 1016) at an average concentration of 100 ng/kg/day, 50 microg/kg/day,
and 50 microg/kg/day, respectively, during Days 16-18 of gestation. A high
dose of DES (200 microg/kg/day) was also tested to compare the results
of the current study with those of others using the high dose only. The
offspring were examined at Day 3, Day 21, and Day 60 following birth. We
demonstrated that BPA, Aroclor, and the lower dose of DES enhanced anogenital
distance, increased prostate size, and decreased epididymal weight.
No effect was found on the testicular weight or size. The chemicals also
permanently
increased androgen receptor (AR) binding activity of the prostate at this
dosage. This is the first demonstration that environmental chemicals
program AR function permanently at the dosage consumed by the general
population. The higher dosage of DES, on the other hand, produced an
opposite effect, decreasing prostate weight, prostate AR binding, and anogenital
distance, thus confirming the previous reports. To investigate whether
the above mentioned effects of the chemicals represent direct or indirect
effects, we also tested the effect of the chemicals on prostate development
in vitro. Thus fetal urogenital sinus (UGS), isolated at the 17th day of
gestation was cultured with the chemicals in the presence and absence of
testosterone (10 ng/ml) for 6 days, and prostate growth was monitored by
determining the size and branching of the specimen following histology.
Results showed that these chemicals induced prostate growth in the presence
and absence of testosterone. They also increased androgen-binding
activity. Thus, the results of the in vivo studies were reproduced
in the in vitro experiments, suggesting a direct effect of these chemicals
on the development of fetal reproductive organs. This is the first demonstration
that estrogenic chemicals induce reproductive malformation by direct
interference with the fetal reproductive organs and not by interfering
with the maternal or fetal endocrine system. The chemicals are able
to induce malformation even in the absence of fetal testosterone; however,
they are more effective in the presence of testosterone. (Gupta,
2000)
Study #2
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PCB 169 resulted in abnormal rodent sex differentiation
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the developing animal is extremely sensitive to toxicants during sex differentiation
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many effects are difficult to detect until late in life
In humans and rodents, exposure to hormonally active chemicals during sex
differentiation can produce morphological pseudohermaphrodism (Schardein,
1993; Gray, 1992). For example, hormonally active drugs like DES (estrogenic),
Danazol (androgenic), and progestins cause urogenital malformations in
the reproductive tracts of humans and rodents. The current discussion will
present new information on the effects of toxic chemicals and pesticides
that act on reproductive development via novel mechanisms, including germ
cell toxicity, antiandrogenicity, and Ah-receptor binding. Information
will be presented that describes how exposure during critical stages of
life to synthetic chemicals present in our environment, such as benzidine-based
dyes, antiandrogenic fungicides, 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD),
and PCB congener 169, result in abnormal rodent sex differentiation.
In rodents, perinatal exposure to fetal germ cell toxicants reduced the
reproductive potential of female, and permanently reduced sperm production
in male progeny. Phenotypic sex differentiation, however, was unaffected
by these germ cell toxicants. In contrast, antiandrogenic drugs and fungicides
induced profound alterations in phenotypic sex differentiation. Effects
such as hypospadias, ectopic testes, vaginal pouches, agenesis of the
ventral prostate, and nipple retention in male rats were observed commonly.
Although these antiandrogens induced no permanent effects in female progeny,
another class of chemicals, the Ah-receptor mediated toxicants, did reduce
fertility in both male and female rat offspring. Cauda epididymal sperm
numbers were reduced permanently in TCDD-exposed male rat and hamster progeny,
and female progeny displayed malformations of the external genitalia. Other
toxicants produced dramatic alterations of sex differentiation (uterus
unicornis, agenesis of the vas and epididymis, and undescended testes),
via mechanisms that have not been characterized yet. Since these adult/pubertal
alterations resulted from gestational and/or neonatal exposures, future
studies should include a comprehensive assessment of reproductive function
after perinatal exposure because the developing animal is extremely
sensitive to toxicants during sex differentiation, and many of the effects
are difficult to detect until late in life. (Gray et al, 1996)
Study #3
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ventral prostate weight was reduced by PCB 126 and especially PCB 105
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PCB 105 affects development of the male reproductive system by mechanisms
in addition to or independent of Ah receptor agonist activity
Experiments were conducted to investigate effects of in utero and lactational
exposure to prototype polychlorinated biphenyls (PCBs) on development of
the male reproductive system. Three congeners were tested: PCB 153 (an
inducer of phenobarbital-responsive enzymes); PCB 105 (a mixed-type inducer
whose major metabolite binds with high affinity to transthyretin); and
PCB 126 (an Ah receptor agonist). Pregnant Holtzman rats were dosed orally
with PCB 153 (5 mg/kg), PCB 105 (2.5 mg/kg), PCB 126 (0.5 ug/kg), or vehicle
(1 mL corn oil/kg) beginning on Gestation Day 6 and continuing daily through
weaning. There was little if any detectable overt toxicity among dams or
pups. Each congener increased relative liver weight and decreased relative
thymus weight in 3- and 9-day old pups. PCB 126 accelerated eye opening,
while PCBs 105 and 126 delayed preputial separation. At postnatal day 63,
ventral prostate weight was reduced by each PCB, while dorsolateral prostate
weight was reduced by PCBs 105 and 126. By postnatal day 161, dorsolateral
prostate weight was normal in all treatment groups but ventral prostate
weight was still reduced by PCB 126 and especially PCB 105. Testis
and epididymis weights and testicular and cauda epididymal sperm counts
in PCB 105-exposed rats were increased 10-12% at postnatal day 161, presumably
due to transient hypothyroxinemia earlier in development. In contrast,
PCB 126 tended to reduce sperm counts. Effects of PCB 105 throughout this
study were generally greater than (or distinct from) those of PCB 126 even
though the daily dose of PCB 126 was the highest that could be given without
substantial pup mortality. Although all effects of PCB 105 would have been
detected by examining endpoints known to be affected by 2,3,7,8-tetrachlorodibenzo-p-dioxin,
these findings suggest that PCB 105 affects development of the male reproductive
system by mechanisms in addition to or independent of Ah receptor agonist
activity. (Moore et al, 1998)
Study #4
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ventral prostate (VP) weight was reduced by 36% in the PCB group
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myeloperoxidase (MPO) activity in the lateral prostate (a measure of inflammation)
was higher
Perinatal exposure to Arochlor 1254 (A1254), a PCB mixture with dioxin-like
activity, has been associated with a variety of alterations in reproductive
development in male rats, ranging from altered testis size to infertility.
Some effects result from hypothyroidism during testis development while
others are likely related to Ah-receptor binding. In this study, timed-pregnant
Sprague-Dawley rats were given 24 mg/kg A1254 (AccuStandard), p.o. daily,
from gestational day 6 through postnatal day (PND) 22. Serum thyroxine
(T4) levels in PCB-exposed pups were depressed to 9% and 12% of controls
on PND 16 and 23, respectively, with partial recovery (42%) at PND 45 and
full recovery by PND 210. Male pups from A1254-treated dams were evaluated
for reproductive performance at approximately PND 120 and found to be fertile,
with litter sizes and fertilization rates not statistically different from
controls (13.7 +/- 1.1, vs. 14.8 +/- 1.0, and 89.4% +/- 7.5 vs. 97.0% +/-
3.0). Upon necropsy (PND 210), testis, epididymal, and lateral prostate
weights, testicular sperm head counts, sperm motion characteristics
(evaluated by CASA), and serum testosterone levels were also comparable
in both groups. However, ventral prostate (VP) weight was reduced by
36% in the PCB group and myeloperoxidase (MPO) activity in the lateral
prostate (a measure of inflammation) was higher. For comparison, two
dams were dosed with 32 mg/kg Aroclor 1254 on PND 1-3, 5, 7, 9 only, a
regimen shown previously to cause infertility in adult male offspring,
as well as increased testis weight and decreased VP weight (Sager,
1983). The male offspring from these litters were comparable to controls
for all measures except lateral prostate MPO activity, which was elevated.
Thus,
perinatal (primarily lactational) exposure to A1254 did not alter testis
size or fertility in male offspring. (Jeffay et al, 1999)
Study #5
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An association was suggested between PCB concentrations in subcutaneous
abdominal adipose tissue and the occurrence of prostate cancer
A. Evidence for carcinogenicity to humans (limited) Information on the
possible carcinogenic risk of human exposure to polychlorinated biphenyls
(PCBs) comes from studies of occupational populations and of populations
exposed to the compounds accidentally. PCB mixtures may be contaminated
with polychlorinated dibenzofurans and polychlorinated dibenzodioxins (see,
e.g, p. 350). A slight increase in the incidence of cancer, particularly
melanoma of the skin, was reported in a small group of men exposed to Aroclor
1254, a mixture of PCBs. In a study of over 2500 US workers exposed to
a similar mixture of PCBs during the manufacture of electrical capacitors,
five deaths due to cancer of the liver and biliary passages were observed,
where as 1.9 would have been expected. This increase was sustained mainly
by female workers in one of the two plants in the study (four of the five
deaths), and all five workers had first been employed before the early
1950s. Another study of workers in a capacitor plant was conducted in Italy.
Exposure in the early years of production (until 1964) was to PCB mixtures
containing 54% chlorine (mainly Aroclor 1254 and Pyralene 1476), which
were later replaced by mixtures containing 42% chlorine (mainly Pyralene
3010 and 3011). Early results showed a significant excess of all cancers
among male workers, which was due mainly to cancers of the digestive system
and of the lymphatic and haematopoietic tissues. Among female workers,
a slight increase in mortality from cancer of the lymphatic and haematopoietic
tissues was reported. The study was later enlarged and extended to include
2100 workers and to cover the period 1946-1982. Both male and female workers
exhibited significantly increased cancer mortality in comparison with rates
for the local population (14 observed, 7.6 expected; and 12 and 5.3, respectively,
for men and women). Among male workers, cancers of the gastrointestinal
tract (two stomach, two pancreas, one liver and one biliary passages) taken
together were significantly increased (6 observed, 2.2 expected). Female
workers showed a significant increase in deaths from haematological neoplasms
(4 observed, 1.1 expected). In Sweden, among 142 male workers employed
between 1965 and 1978 in a capacitor manufacturing plant when PCB mixtures
containing up to 42% chlorine had been used, no significant excess of cancer
deaths was noted. Cancer incidence was also examined: the number of cases
observed corresponded well to that expected. One individual in a subgroup
with higher exposure developed two relatively rare tumours, both of which
occurred ten years after the start of exposure: a slow-growing mesenchymal
tumour (desmoid) and a malignant lymphoma. After contamination of cooking
oil with a mixture of PCBs (Kanechlor 400) in Japan in 1968, a large population
was intoxicated ('Yusho' disease). An early report on mortality from 1963-1983
showed a significantly increased risk of all cancers, and an almost five-fold
significantly elevated risk of primary liver cancer. The edible rice oil
had also been contaminated by polychlorinated quaterphenyls and polychlorinated
dibenzofurans. Dose response relationships were not clarified. A further
comprehensive study of 887 male 'Yusho' patients showed statistically significantly
increased mortality from all malignancies (33 observed, 15.5 expected),
from liver cancer (9 observed, 1.6 expected) and from lung cancer (8 observed,
2.5 expected). Use of local rather than national rates in calculating expected
number of deaths decreased the observed:expected ratio for liver cancer
from 5.6 to 3.9, which was still statistically significant. A closer look
at the geographical distribution of liver cancer cases did not allow exclusion
of factors other than PCB poisoning as a possible explanation for this
finding. For the 874 female patients examined, none of the noted observed:expected
ratios was significant. In a series of ten autopsies of 'Yusho' patients,
two adenocarcinomas of the liver were found, with no indication of a direct
association with exposure to PCBs. Ultrasonic and tumour marker examination
of two series of 79 and 125 patients with 'Yusho' disease in 1983 and 1984,
respectively, did not reveal any case of hepatic-cell carcinoma. Two studies
of the PCB content of fat tissues and cancer occurrence were available.
An
association was suggested between PCB concentrations in subcutaneous abdominal
adipose tissue and the occurrence of cancers of the stomach, colon,
pancreas, ovaries and prostate. No indication emerged of a relationship
between PCB content in extractable breast fat tissue and the occurrence
of breast cancer. The available studies suggest an association between
cancer and exposure to PCBs. The increased risk from hepatobiliary cancer
emerged consistently in different studies. Since, however, the numbers
were small, dose-response relationships could not be evaluated, and the
role of compounds other than PCBs could not be excluded, the evidence was
considered to be limited. B. Evidence for carcinogenicity to animals (sufficient)
Certain PCBs (particularly with greater than 50% chlorination) produced
benign and malignant liver neoplasms in mice and rats after their oral
administration. Oral administration of Aroclor 1254 to rats yielded hepatocellular
adenomas and carcinomas as well as intestinal metaplasia and a low, statistically
nonsignificant incidence of stomach adenocarcinomas. PCBs were inadequately
tested in mice for induction of skin tumours. In several studies, oral
or intraperitoneal administration of PCBs enhanced the incidences of preneoplastic
lesions and of neoplasms of the liver induced in rats by N-nitrosodiethylamine
or 2-acetylaminofluorene. In one study, intragastric administration of
PCBs to mice increased the incidence of lung tumours induced by intraperitoneal
administration of N-nitrosodimethylamine. C. Other relevant data No data
were available on the genetic and related effects of PCBs in humans. Dominant
lethal effects were not induced in rats administered PCBs orally, but were
produced in rats nursed by females that had received PCBs orally. PCBs
did not induce chromosomal aberrations in bone-marrow cells or spermatagonia
of rats treated in vivo; micronuclei were not induced in bone-marrow cells
of mice in one study, while equivocal results were obtained in a second
study in which the PCBs were administered in corn oil. They did not transform
Syrian hamster embryo cells in vitro. PCBs induced DNA strand breaks and
unscheduled DNA synthesis in rat hepatocytes in vitro. Neither chromosomal
breakage nor aneuploidy was induced in Drosophila. PCB mixtures did not
induce SOS repair and were not mutagenic to bacteria. 2,2',5,5'-Tetrachlorobiphenyl
induced DNA strand breaks in mouse cells in vitro. 2,4,5,2',4',5'-Hexachlorobiphenyl
but not 3,4,5,3',4',5'-hexachlorobiphenyl inhibited intercellular communication
in Chinese hamster V79 cells. Purified 2,4,2',4'-, 2,5,2',5'- and 3,4,3',4'-tetrachloro-
and 2,4,6,2',4',6'-hexachlorobiphenyl were not mutagenic to bacteria.
(IARC 1987)
Study #6
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PCBs increased enzyme activities in rat prostates, in a more pronounced
fashion than other inducing chemicals
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prostate sensitivity to PCB enzyme induction and the capacity of the prostate
to produce mutagenic metabolites might be of importance for initiation
of prostatic cancer by environmental factors.
Induction of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin-O-deethylase
(7-EOD) activities as well as of benzo(a)pyrene (BP) metabolite formation
in rat prostatic microsomes was demonstrated after treatment with beta-naphthoflavone
(BNF). The capacity to convert promutagenic compounds to ultimate mutagenic
metabolite in the Ames' Salmonella assay by 5000nvestigated. Male rats
were treated with BNF, polychlorinated biphenyls (PCB; Arochlor 1254),
phenobarbital (PB) and the vehicle, corn oil. PCB or BNF pretreatment
increased the AHH- and 7-EOD activities 100- to 200-fold in the rat prostate
5000upernatant (S-5 fraction). Epoxide hydrolase (EH) and glutathione-S-transferase
(GST) activities were not affected while UDP-glucuronosyltransferase
(UDP-GT) was increased 2.2- and 2.5-fold by PCB and BNF,
respectively. PB did not significantly affect any of the enzyme activities
measured. A dose-dependent increase in mutagenic response vs. amount of
5000promutagen (aflatoxin B1 (AFB), 2-aminofluorene (2-AF), BP) was observed.
The
most pronounced activation was obtained with S-5 fraction from BNF-
or PCB-treated rats. The great sensitivity of prostatic AHH to certain
inducers and the capacity of the prostate to produce mutagenic metabolites
might be of importance for initiation of prostatic cancer by environmental
factors. (Soderkvist et al, 1983)
Study #7
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PCB metabolites [breakdown products] have been found in the ventral prostate
Studies of the tissue distribution of polychlorinated biphenyls (1336363)
(PCBs) in laboratory animals were summarized. Twenty eight PCBs and six
chlorinated compounds which are not PCBs were investigated. Studies of
the distribution of carbon-14 labeled PCBs in mice were discussed. Dose
and structure dependent accumulation and long term retention of the compounds
in the tracheobronchial mucosa have been observed. The greatest accumulation
occurred in PCBs having chlorines in the 2,2',4,4',5,5' positions. Most
of the PCBs were present as 4-methylsulfonyl metabolites. Radiolabeling
studies have indicated that the 4-methylsulfonyl PCB (MeSOPCB) metabolites
are bound initially to a specific MeSOPCB binding protein in the Clara
and goblet cells. This proteineSOPCB complex has been shown to be subsequently
secreted into the airway lumen and spread over the entire surface lining.
Studies on the accumulation of MeSOPCBs in kidney proximal tubular cells
in mice were discussed. These have shown that the extent of accumulation
is different from that of the lung, and apparently depends on the nature
of the substituent in the para position. Accumulation of PCB metabolites
in sites outside the lung and kidney were discussed. MeSOPCBs have been
found in the uterine and fetal soft tissues of mice, the ventral
prostate and large intestinal epithelium of rats, and the cerebral
gray matter of quail. Tissue binding of sulfur containing PCBs which are
not xenobiotics was considered. Studies with dimethylsulphone (67710) and
chlorinated benzenes in mice have shown that sulfur containing metabolites
accumulate in the lung, kidney, liver and adrenal cortex. (Brandt
et al, 1987)
Study #8
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prostate weights (g) were slightly increased in the PC60 group at the 1st
and 4th week following treatment
1 The aim of this study was to ascertain the reproductive effects of PCB
77 on adult male rats and to determine its concentration in the liver and
testis. Adult male rats (n = 15/group) were treated subcutaneously with
a single dose of 18 mg/kg bw (PC18) or with 60 mg/kg bw (PC60). The substance
was dissolved in a 10 ml volume of peanut oil/kg. Control rats received
the same volume of the vehicle. The reproductive effects as well as the
concentration of PCB 77 in the liver and testis were investigated 1, 4
and 8 weeks after treatment. 2 In both groups, the daily sperm production
(DSP; x10(6)) remained permanently reduced in the PC18 as well as in the
PC60 groups throughout the entire investigation period (DSP week 8: control:
31 +/- 7; PC18: 22 +/- 5; PC60: 20 +/- 7). The sperm number (x10(6)) per
cauda epididymis was affected only at the 1st and 4th week after treatment
(control week 1: 211 +/- 67; PC18 week 1: 135 +/- 62; PC60 week 1: 142
+/- 49). Moreover, a significant increase in the percentage of abnormal
sperm was observed 4 weeks following treatment in the PC18 and PC60 groups
and 8 weeks after treatment in the PC60 group. Abnormal tails were the
most frequent changes observed. 3 The relative testicular and prostate
weights (g) were slightly increased in the PC60 group at the 1st and
4th week following treatment (testis weight: control/I: 0.46 +/- 0.02;
PC60/I: 0.51 +/- 0.03). 4 The serum testosterone concentrations and effects
on testis morphology were not reported. 5 The maximum concentration of
PCB 77 was detected in the liver and testis 1 week after treatment. The
concentration declined 4 weeks after treatment in both organs, but still
a significant amount of PCB 77 was detectable in the liver as well as in
the testis 8 weeks after treatment. 6 The results demonstrate that PCB
77 affects sperm variables when applied to adult rats and that the elimination
of PCB 77 in the testis parallels that of the liver. (Faqi et al,
1998a)
Study #9
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ventral prostate weights permanently reduced in PCB 126 treated male rats
1. Pregnant Wistar rats were treated orally with a single dose of 100 microg
3,3',4,4'-tetrachlorobiphenyl (PCB 77)/kg b.w. or 10 microg 3,3',4,4',5
pentachlorobiphenyl (PCB 126)/kg b.w. on day 15 of pregnancy. The control
rats received peanut oil at the same day. Developmental landmarks were
assessed in all offspring rats and reproductive effects of PCB 77 and PCB
126 on male offspring were studied on postnatal day 65 (at puberty) and
on postnatal day 140 (at adulthood). 2. The ano-genital distance as well
as the ratio ano-genital distance to body length was reduced in male pups
of the PCB 126 group and the age at vaginal opening was significantly delayed
in the female pups. 3. Testis, brain weights and daily sperm production
were permanently increased and seminal vesicle weights were decreased in
male offspring of the PCB 77 group. In male rats of PCB 126 group,
the brain weights were permanently increased and ventral prostate weights
permanently reduced. In both PCB groups, however, serum testosterone
concentration was reduced only at adulthood. Additionally, the male rats
of the PCB 126 group showed alterations in sexual behavior. In these rats
the number of mounts with intromissions was significantly increased. 4.
The results of this study show that PCB 126 elicits some TCDD-like reproductive
effects after in utero exposure, while the reproductive effects of in utero
exposure to PCB 77 on male offspring may be attributed to the neonatal
hypothyroidism induced by the substance during early fetal development.
Further studies using multiple doses and providing thyroid hormone data
will be necessary to support this hypothesis. (Faqi et al, 1998b)
Study #10
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ventral prostate weights in all experimental male offspring were significantly
less than those of controls
Effects of the early administration of polychlorinated biphenyls (1336363)
(PCBs) on adult fertility and the condition of sexual accessory glands
in males were investigated using sperm positive pregnant rats. The PCB
Aroclor-1254 (11097691) was administered by oral intubation to lactating
dams on days one through three, five, seven, and nine postpartum. Treatment
groups received 0, 8, 32, or 64mg/kg doses. Male offspring were autopsied
at 165 days of age, at least 8 days after mating. The average number of
fetuses was significantly less and the average number of implantations
was reduced among normal virgin females mated to male offspring exposed
to the two higher dose levels of PCBs. Resorption rate among these females
was also higher and fewer of them became pregnant after exposure to males.
Ventral
prostate weights in all experimental male offspring were significantly
less than those of controls. Fewer numbers of alveoli, less folding
of the mucosa, and flattened epithelial cells in the alveoli were noted
on microscopical examination of these glands. PCB residues were found in
both liver and adipose tissue of all experimental offspring, even though
they had not received PCBs since weaning, a period of about 20 weeks. Weight
gain in litters exposed to the two higher dose levels was significantly
less during days one through 11 of lactation, but subsequent weight gain
was normal. Five offspring of the highest dose level group developed a
toxic syndrome characterized by loss of hair, weight loss, and a swollen
abdomen, culminating in death. The author concludes that early exposure
to PCBs results in damage to the reproductive system in these animals.
(Sager, 1983)
Study #11
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low but detectable amounts of PCB metabolites were found in cytosolic preparations
from prostate
When a 3H-labeled metabolite of polychlorinated biphenyls (PCB), 4,4'-bis(3H)methylsulfonyl)-2,2'-5,5'-tetrachlorobiphenyl
((3H-MeSO2)2TCB) was administered i.p. to rats, a selective labeling was
registered in the apical cytoplasm of the nonciliated bronchiolar (Clara)
cells of the lung as determined by microautoradiography of sections of
methacrylate-embedded tissue. (Polychlorinated biphenyls are industrial
chemicals which have become widespread environmental pollutants). In vitro,
(3H-MeSO2)2TCB bound with high affinity (Kd = 2.5-15 nM) and high capacity
(Bmax (maximum number of binding sites) = 30-70 pmol/mg of protein) to
rat lung cytosol. Binding of (3H-MeSo2)2TCB to the high affinity sites
was temperature dependent, reversible and saturable. The sites seemed to
reside within a protein-like component, since proteolytic enzymes significantly
reduced the binding. Physicochemical characterization of the (3H-MeSO2)2TCB-binding
protein indicated a Stokes radius of 22 of these parameters, an apparent
MW of 16,000 was calculated. The binding entity had an apparent pI (negative
log of ionization constant) of 5.3 and eluted as a single radioactive peak
from CM (carboxymethyl)-Sepharose at 75 mM acetate. Binding with similar
affinities (IC50 (concentration giving 50% inhibition) values, 4-65 nM)
was shown to occur also with other PCB methyl sulfones, whereas only one
PCB, 2,2',4,4',5,5'-hexachlorobiphenyl, competed for (3H-MeSO2)2TCB binding,
but with a lower affinity (IC50 = 3 muM). Among other compounds tested,
only progesterone and some derivatives thereof displayed an affinity for
the (3H-MeSO2)2TCB-binding protein (IC50 values ranging from 1-10 muM).
Lung cytosol showed by far the highest amount of specific (3H-MeSO2)2TCB
binding. Low but detectable amounts were also found in cytosolic preparations
from prostate, kidney and large intestine. (3H-MeSO2)2TCB also bound
to an entity in mouse lung cytosol with the same physicochemical characteristics
as that in rat lung cytosol and to a progesterone-binding protein purified
from rabbit uterus (uteroglobin). Rat lung contains a uteroglobin-like
macromolecule with a pronounced affinity for at least certain PCB methyl
sulfones. This binding entity apparently is responsible for the striking
accumulation of such metabolites in lung tissue following administration
of PCB to rats and mice. (Lund et al, 1985)
Study #12
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furans significantly decreased ventral prostate weights [PCBs are generally
contaminated with furans]
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furans are more toxic substances than PCBs when administered to rats
The toxic effects of polychlorinated biphenyl (PCB) mixtures and polychlorinated
dibenzofurans (PCDF) were compared on male SD-derived rats fed diets containing
100 ppm of PCB and 1 or 10 ppm of PCDF for 4 wk. Rats fed 10 ppm diets
of PCDF developed chloracne-like lesions on the ears within 3 wk. PCDF
markedly and PCB slightly depressed body weight gain. In rats fed diets
containing 10 ppm of PCDF, significantly decreased thymus, ventral
prostate and seminal vesicle weights were found. Hg and hematocrit
values were decreased in rats fed either diet containing PCDF. PCB produced
very minimal effects on thymus and accessory sex organ weights and hematologic
values. Both PCB and PCDF increased serum cholesterol concentrations and
cholinesterase activity and decreased triglyceride concentrations and leucine
aminopeptidase activity. PCDF decreased serum glutamic-pyruvic transaminase
activity and testosterone concentration in testis and increased serum glutamic-oxaloacetic
transaminase activity. In the rat, PCDF are more toxic substances than
PCB when administered in the diet. (Oishi et al, 1978)
Study #13
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PCB-126 had no effect on the androgen receptor content of the prostate
3,3',4,4',5-Pentachlorobiphenyl (PCB 126) and 2,2',4,4',5,5'-hexachlorobiphenyl
(PCB 153) were administered to adult male rats in order to identify sensitive
indicators of endocrine disruption. We tested the hypothesis that PCB exposure
modifies follicle-stimulating hormone (FSH) pituitary isoforms, as well
as the pituitary and serum concentrations of FSH, luteinizing hormone (LH),
growth hormone, prolactin, and thyroid-stimulating hormone (TSH). Effects
on serum levels of thyroxine (T4) and tes ghest dose group. In contrast,
pituitary content of FSH and LH increased with PCB-126 doses (p =0.004,
p = 0.002, respectively). Despite changes in reproductive hormones, PCB-126
had no effect on the androgen receptor content of the prostate. The
effect of PCB-126 was tested in the hemicastrated rat, and suggested adverse
effects on testosterone secretion. To test the effects of PCB exposure
on FSH pituitary isoforms, 4 groups of 10 male rats received two ip injections,
one day a (abstract imcomplete) (Desaulniers et al, 1999)
Study #14
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dioxin enhanced AHH enzyme activity in the prostate [PCBs are frequently
contaminated with dioxins]
The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (1746016) (TCDD), polychlorinated
dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) on aryl-hydrocarbon-hydroxylase
(AHH) inducing potency were studied in rats. Male Wistar-rats were administered
5 micrograms per kilogram (microg/kg) TCDD intraperitoneally (ip), 5microg/kg
of an isomeric mixture of 15 PCDFs ip, or 50 milligrams per kilogram ip
of a commercial PCB preparation containing approximately 54 percent chlorine
(7782505). The animals were observed for signs of toxicity. The rats were
killed 3 days after treatment and liver, lung, kidney, prostrate, thymus,
and spleen sections were removed and assayed for basal and induced AHH
activity. Only TCDD enhanced AHH activity in the prostate, thymus,
and spleen. All compounds increased hepatic AHH activity. TCDD was the
most potent inducer of AHH activity in all six organs. PCDFs significantly
enhanced AHH activity in the liver and lung. The authors conclude that
PCDFs are more potent inducers of AHH activity in the lung and liver than
PCBs. Their potency in those organs is comparable to that of TCDD. Chlorinating
the number 1 position in the dibenzofuran ring reduces the ability of PCDFs
to enhance AHH activity. PCDFs with chlorine atoms in positions 2, 3, 7,
and 8 seem to have the highest toxicity. (Nagayama et al, 1983)
Study #15
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the effects of PCB 169 bear little resemblance to those of any known anti-androgen
Antiandrogenic chemicals alter sexual differentiation by a variety of mechanisms,
and as a consequence, they induce different profiles of effects. For example,
in utero treatment with the androgen receptor (AR) antagonist, flutamide,
produces ventral prostate agenesis and testicular nondescent, while
in contrast, finasteride, an inhibitor of 5 alpha-dihydrotestosterone (DHT)
synthesis, rarely, if ever, induces such malformations. In this regard,
it was recently proposed that dibutyl phthalate (DBP) alters reproductive
development by a different mechanism of action than flutamide or vinclozolin
(V), which are AR antagonists, because the male offsprings display an unusually
high incidence of testicular and epididymal alterations--effects rarely
seen after in utero flutamide or V treatment. In this study, we present
original data describing the reproductive effects of 10 known or suspected
anti-androgens, including a Leydig cell toxicant ethane dimethane sulphonate
(EDS, 50 mg kg-1 day-1), linuron (L, 100 mg kg-1 day-1), p,p'-DDE (100
mg kg-1 day-1), ketoconazole (12-50 mg kg-1 day-1), procymidone (P, 100
mg kg-1 day-1), chlozolinate (100 mg kg-1 day-1), iprodione (100 mg kg-1
day-1), DBP (500 mg kg-1 day-1), diethylhexyl phthalate (DEHP, 750 mg kg-1
day-1), and polychlorinated biphenyl (PCB) congener no. 169 (single
dose of 1.8 mg kg-1). Our analysis indicates that the chemicals discussed
here can be clustered into three or four separate groups, based on the
resulting profiles of reproductive effects. Vinclozolin, P, and DDE, known
AR ligands, produce similar profiles of toxicity. However, p,p'-DDE is
less potent in this regard. DBP and DEHP produce a profile distinct from
the above AR ligands. Male offsprings display a higher incidence of epididymal
and testicular lesions than generally seen with flutamide, P, or V even
at high dosage levels. Linuron treatment induced a level of external effects
consistent with its low affinity for AR [reduced anogenital distance (AGD),
retained nipples, and a low incidence of hypospadias]. However, L treatment
also induced an unanticipated degree of malformed epididymides and testis
atrophy. In fact, the profile of effects induced by L was similar to that
seen with DBP. These results suggest that L may display several mechanisms
of endocrine toxicity, one of which involves AR binding. Chlozolinate and
iprodione did not produce any signs of maternal or fetal endocrine toxicity
at 100 mg kg-1 day-1. EDS produced severe maternal toxicity and a 45% reduction
in size at birth, which resulted in the death of all neonates by 5 days
of age. However, EDS only reduced AGD in male pups by 15%. Ketoconazole
did not demasculinize or feminize males but rather displayed anti-hormonal
activities, apparently by inhibiting ovarian hormone synthesis, which resulted
in delayed delivery and whole litter loss. In summary, the above in vivo
data suggest that the chemicals we studied alter male sexual differentiation
via different mechanisms. The anti-androgens V, P, and p,p'-DDE produce
flutamide-like profiles that are distinct from those seen with DBP, DEHP,
and L. The effects of PCB 169 bear little resemblance to those of any
known anti-androgen. Only in depth in vitro studies will reveal the
degree to which one can rely upon in vivo studies, like those presented
here, to predict the cellular and molecular mechanisms of developmental
toxicity. (Gray et al, 1999)
Study #16
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endocrine disrupting chemicals [such as PCBs] operate during critical period
(s) in the early stage of life characterized by rapid cell differentiation
and organogenesis, leaving irreversible disruption
-
endocrine disrupting chemicals [such as PCBs] may not demonstrate any clear
minimum threshold in exerting their "toxicological" effects
-
endocrine disrupting chemicals [such as PCBs] may act synergistically or
additively with other chemicals
Endocrine disrupting chemicals (EDCs) seem to be different from classic
environmental toxicants in several points: 1) EDCs operate during critical
period (s) in the early stage of life characterized by rapid cell differentiation
and organogenesis, leaving irreversible disruption thereof. 2) EDCs may
not demonstrate any clear threshold in exerting its "toxicological" effects
and 3) EDCs may act synergistically or additively. Except for few cases
such as diethylstilbestrol causing cancer in female offspring, a clear
cause effect relationship between cancers in humans and EDCs is still hard
to demonstrate. Thanks to continual epidemiological endeavors, a few
reports suggest such a relationship between prostate cancer and herbicides.
Because of its frequent association in incidence with inborn abnormalities
of male reproductive organs such as undescended testis, hypospadias and
degenerated quality of sperm, testicular cancer is suspected to have common
or related pathogenesis with them. A hypothesis advanced by Carlsen et
al was introduced. (Ohi, 1999)
Study #17
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firefighters face increased prostate cancer risks, after chemical exposures
which often include PCBs and furans
There is a considerable body of information available concerning the carcinogenic
hazards of firefighting and attention has been given to specific toxic
and carcinogenic chemical exposures. Firefighters are routinely exposed
to complex and dynamic mixtures of chemical substances that are contained
in fire smoke and building debris. Specific attention was given in this
review to exposure to benzene (71432), asbestos (1332214), polycyclic aromatic
hydrocarbons, formaldehyde (50000), diesel exhaust, polychlorinated
biphenyls, furans, styrene (100425), and methylene-chloride (75092).
As exposures to these agents are intermittent and variable, the significance
of the exposures is still unresolved. Prevalent cancers in firefighters
and associations with carcinogenic occupational exposures were discussed
in light of 19 epidemiologic studies of cancer in these workers. The findings
indicated that employment as a firefighter increases the risk of developing
and dying from leukemia, non-Hodgkin's lymphoma, multiple myeloma, and
cancers of the brain, urinary bladder, and possibly from cancer of the
prostate, large intestine, and skin. (Golden et al, 1995)
Study #18
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prostate cells were used to test endocrine disrupting chemicals, such as
PCBs
-
disturbed male sexual differentiation may in some cases be caused by increased
exposure to environmental xenoestrogens and/or antiandrogens [such as PCBs]
Over the past 20 years, the documented increase in the disorders of male
sexual differentiation, such as hypospadias, cryptorchidism, and micropenis,
has led to the suspicion that environmental chemicals are detrimental to
normal male genital development in utero. Male sexual differentiation is
critically dependent on the normal action of androgens, and unbalanced
androgen/estrogen ratios can disturb it. Environmental xenoestrogens (such
as herbicides, pesticides, PCBs, plasticizers, and polystyrenes)
that mimic estrogens or environmental antiandrogens (such as polyaromatic
hydrocarbons, linuron, vinclozolin, and pp'DDE) that disturb endocrine
balance, cause demasculinizing effects in the male foetus. These
environmental chemicals are often referred to as endocrine disruptors:
they are thought to mimic endogenous estrogens by entering the cell, binding
to the receptor and activating transcription, they may also antagonize
normal androgen action. We have established numerous cell lines to assess
the estrogenicity and antiandrogenicity of compounds found in the environment
and to identify new products present in wastewater effluents that are able
to disrupt endocrine functions. Several cell lines responding to estrogens
have been obtained in our group, including cells with different enzymatic
equipment and cells expressing chimeric receptor or natural estrogen receptors
alpha and beta. These cell lines have proved to be useful for assessing
the biological activity of pesticides, fungicides, and chemicals found
in plastic or discarded in the environment. In order to generate a powerful
tool for the investigation of androgen action and the rapid screening of
potential antagonists, we developed a new stable prostatic cell line.
The PALM cell line is an original cellular model to characterize the response
of hAR, and it provides an easy and rapid bioluminescent test to identify
new antagonists. We also developed a model based on a fusion protein between
the androgen receptor (AR) and the green fluorescent protein (GFP) to study
the intracellular dynamics of AR. The GFP-AR model was applied to define
the ability of several xenoestrogens and antiandrogens to inhibit the nuclear
transfer of AR. The ubiquitous presence of endocrine disruptors in the
environment and the increased incidence of neonatal genital malformation
support the hypothesis that disturbed male sexual differentiation may in
some cases be caused by increased exposure to environmental xenoestrogens
and/or antiandrogens. (Sultan et al, 2001)
Study #19
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PCBs are metabolically activated to electrophilic quinoid species capable
of binding to DNA
-
PCB metabolites are capable of redox cycling, thereby increasing oxidative
stress in biological systems
-
PCB congeners form DNA adducts after metabolic activation
-
this study could not detect PCB DNA effects in live rats
It is known that lower-chlorinated biphenyls are metabolically activated
to electrophilic quinoid species capable of binding to DNA. Also, certain
metabolites are capable of redox cycling, thereby increasing oxidative
stress in biological systems. In the present study, we tested mono-,
di-, tri-, tetra-, penta-, hexa-, and heptachlorinated biphenyls for their
ability to bind with DNA and to induce oxidative DNA damage. We present
additional evidence that several PCB congeners form DNA adducts after
metabolic activation, which can be detected by the nuclease P1- or
butanol-enrichment procedures of the (32)P-postlabeling technique. Butanol
and nuclease P1 enrichments showed different adduct recoveries, depending
on the level of chlorination of the biphenyls. Application of the nuclease
P1 enrichment showed that the incubation of 2-chloro-; 3, 4-dichloro-;
2,4,4'-trichloro-; 3,4,5-trichloro-; and 2,2',5, 5'-tetrachlorobiphenyl
with calf thymus DNA and liver microsomes from rats treated with phenobarbital,
followed by oxidation with a peroxidase, produced five to eight different
DNA adducts. For these lower-chlorinated biphenyls, butanol enrichment
generally showed a lower recovery. For some higher substituted congeners
(3,3',4,4', 5-pentachloro-, 2,2',3,4,4',5'-hexachloro-, 2,2',4,4',5, 5'-hexachloro-,
and 2,2',3,4,4',5,5'-heptachlorobiphenyl), after butanol enrichment a single
dominant spot was observed, which was absent in the nuclease P1 procedure.
After incubation of calf thymus DNA with either higher- or lower-chlorinated
PCB congeners, we were not able to detect significantly increased levels
of oxidative DNA damage above background levels, measured as 8-oxo-7, 8-dihydro-2'deoxyguanosine.
In view of the carcinogenicity of PCB mixtures in animals and the ability
of PCB metabolites to bind covalently to DNA, rats were orally treated
with a mixture of PCBs (Aroclor 1242). PCB-DNA adduct levels were analyzed
in PCB target organs: liver, thymus, glandular stomach, spleen, testes,
seminal vesicles and prostate DNA. In vivo PCB-DNA adducts could
not be detected by either the butanol- or by the NP1-enrichment procedure
in rat target tissue DNA. Also, no differences in oxidative DNA damage
could be observed between PCB-treated rats and controls. These results
indicate a lack of DNA reactivity of PCB mixtures in vivo. (Schilderman
et al, 2000)
Study #20
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PCBs may be a key factor in prostate cancer
Considering the worldwide threat to health and reproduction related to
endocrine disruptors (by-products of the chemical industry); considering
the untrammelled development of the industrialization and engineering of
the living, ethics and gynaecology/obstetrics itself is at a crossroads.
Endocrine disruptors (derived from organochlorines and persistent organic
pollutants such as PCBs, dioxins and furans, and pesticides such
as aldrin, chlordane and DDT), are prime suspects in the deterioration
of fertility and intellectual faculties and possibly a key factor in
endometriosis,
breast cancer and prostate cancer. The long-term and pernicious
impacts of endocrine disruptors show our poor understanding of the complexities
of life's mechanisms. Paradoxically, with our short-term perspectives and
predilection for a technological fix, the problem posed by endocrine disruptors
may accelerate the use of reproductive technologies such as ICSI and even
cloning, as well as the dissemination of genetically modified organisms.
The cure could be worse than the disease. Given the gravity of the challenge
to humanity related to the chemical erosion of human health, the mutation
of human conception introduced by reproductive technologies and by the
drive to genetically modify nature and even human nature, we must urgently
re-evaluate the direction in which our societies are headed and the reliance
on profit-oriented technology to save us from ourselves. In these circumstances,
the collective exercise of wisdom, prudence and responsibility towards
the essence and integrity of humanity has become, more than ever, an ethical,
and perhaps even a survival, imperative. (Vandelac et al, 1999)
Study #21
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PCBs dramatically increased certain steroid hormones (but not others) in
rat prostate tissues
Rat cytochrome P-450 3 (P-450 3) is a constitutive hepatic steroid hormone
7 alpha-hydroxylase which is relatively unresponsive to a number of monooxygenase-inducing
agents. The present study demonstrates that a polyhalogenated aromatic
hydrocarbon inducer, 3,4,5,3',4',5'-hexachlorobiphenyl (HCB), induces
P-450 3 in livers of adult male rats, and that the increase is the result
of an increase in the mRNA for this enzyme. Cytochrome P-450 3 and its
mRNA were increased more slowly and to a lesser extent than cytochrome
P-450c (P-450c) and its mRNA, indicating that these enzymes are not regulated
coordinately in liver. The maximum increase in P-450 3 and P-450 3-dependent
androstenedione 7 alpha-hydroxylase activity (2- to 3-fold) occurred 7
days after administration of HCB, in contrast to the increase in P-450c
(greater than 200-fold) which was maximal by 3-5 days. The rate of induction
of P-450 3 mRNA was also slower [maximum increase (9-fold) at 5 days after
HCB administration] than that of P-450c mRNA [maximum increase (30-fold)
at 2-3 days]. Moreover, a higher dose of HCB was required to produce maximum
induction of P-450 3 (50 mg/kg) than that required to produce maximum induction
of P-450c (10 mg/kg). P-450 3 was not detected on Western blots of lung,
kidney, or prostate microsomes isolated from control or HCB-treated rats
(less than or equal to 2% of that found in livers of HCB-treated rats).
Moreover, P-450 3-dependent steroid 7 alpha-hydroxylase activity was not
detected in these extrahepatic tissues of control or HCB-treated rats (less
than or equal to 1% of that found in the corresponding liver microsomes
of untreated or HCB-treated rats). In contrast, P-450c was increased
dramatically by HCB in lung, kidney, and prostate tissues, indicating
differential expression of P-450c and P-450 3 in extrahepatic tissues.
(Yeowell et al, 1988)
Study #22
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cancer risk is higher for people born during the 1950s than for those born
in 1873-82
-
men face a cancer risk three times higher than before
There is controversy about cancer mortality trends; some analyses show
increasing mortality, but others suggest that rates are falling in the
youngest age groups. We have investigated trends in cancer incidence in
the whole of Sweden for the period 1958 to 1987. 837,085 cancer cases were
registered during the period studied. Incidence rate patterns were studied
by age-period-cohort modelling. The risk of cancer was higher for people
born during the 1950s than for these born in 1873-82; for women the
risk was doubled and for men it was trebled. Although the rate of
increase slowed, it showed no sign of levelling off in the youngest birth
cohorts. The frequency of smoking-related cancers increased greatly in
both sexes, but such tumors could explain only part of the rise in total
cancer. These trends predict a continuing rise in the incidence rate of
cancer, and suggest a worrying pattern of increasing population exposure
to carcinogenic influences. (Adami et al, 1993)
Upcoming Studies
SHIVERICK KT. PLACENTAL/UTERINE & PROSTATE EFFECTS OF ORGANOCHLORINES.
Crisp Data Base National Institutes of Health. Author Address: UNIVERSITY
OF FLORIDA, 1600 SW ARCHER RD, BOX 100485, GAINESVILLE, FL 32610
-
human prostate cell lines may be targeted by PCBs for changes in proliferation,
migration and growth factor gene expression, which may be mechanisms for
the promotion of prostate disease
A primary goal of our research is the identification of alterations in
gene expression in human reproductive cell lines which are mediated by
prototype Superfund chemicals. Our focus is to develop in vitro models
to reproduce some of the in vivo events involved in the development and
function of human placenta, uterus and prostate. In the present funding
period, studies have focused on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD),
benzo(a)pyrene (BaP), and the polychlorinated biphenyl (PCB) congeners
3,3',4,4'-tetrachlorobiphenyl (TCB) and 2,2'4,4'5,5'- hexachlorobiphenyl
(HCB) as prototypes for defining Ah receptor (AhR)- dependent effects.
Our hypothesis is that TCDD, PCBs and BaP alter paracrine and autocrine
growth regulatory networks which are recognized to be important for proliferation,
migration/invasiveness and hormone responsiveness. Dose-response relationships
have been established for each gene product to identify which endpoints
are the most sensitive biomarkers in relationship to the induction of cytochrome
P450 CYPIA1. The next funding period will focus on evaluation of the effects
of PCB congeners which are relevant to human exposure and which may have
both AhR-dependent and -independent mechanisms of action. The first Specific
Aim is to identify mechanisms by which TCDD, PCBs and BaP induce the expression
of the pro-inflammatory cytokines in human uterine and placental cell lines
which may underlie the promotion of uterine disease and impaired placental
development. The second Specific Aim is to characterize the effects of
TCDD, PCBs and BaP on the migration/ invasive activity of placental and
uterine cells relative to changes in cell adhesion molecule interactions
with extracellular matrix and cytoskeletal microfilaments. The Third Aim
is to investigate the potential role of the enzymes prostaglandin H synthase
(PGHS)-1 and -2 in the metabolic activation and toxic effects of BaP and
PCB compounds. PGHS enzymes, constitutively expressed and induced, may
provide an alternative pathway to CYPIAI for peroxidative metabolism and
oxidative stress-induced alterations in gene expression. The final Aim
will investigate whether human prostate cell lines are targets for changes
in proliferation, migration and growth factor gene expression, which can
be mechanisms for the promotion of prostate disease. In summary, this research
will identify and validate sensitive biomarkers for exposure, as well as
establish molecular and cellular mechanisms for altered uterine, placental
and prostate function.
Walther, Philip J., M.D., Ph.D. Prostate Cancer Case-Control Study:
Black vs White VA vs Private Sector. Corporate Name: 119575, 7024, 558
Source: Department of Veterans Affairs_Research and Development, 810 Vermont
Ave. N.W., Washington, D.C., United States of America. Keywords:
PROSTATIC NEOPLASMS; ENVIRONMENTAL EXPOSURE; CASE-CONTROL STUDIES
-
both genetic and environmental factors may contribute to the racial differential
in both incidence and mortality of prostate cancer among blacks and whites
-
gene-environmental interactions initiate and promote prostatic neoplasia
Prostate cancer is the most commonly diagnosed cancer in American men.
Among African Americans the incidence and mortality from prostate cancer
is even greater. Although southern incidence rates tend only to be slightly
higher than that of the nation, a clear discrepancy exists between national
mortality rates and those in the southeast. Notably high rates, particularly
among blacks are observed and in North Carolina the prostate cancer mortality
rate among blacks is the highest of any state in the nation. In spite of
these statistics, very little is known about the etiology of this disease.
The proposed study will build on to an ongoing, NCI-funded, case-control
study in a 63-county area of North Carolina and is proposed to address
questions concerning the differential incidence and mortality of prostate
cancer in black and white men as well as whether there are differences
in patterns of care, risk factors or health related knowledge and beliefs.
In the proposed study we will expand this effort and explore these issues
among men receiving health care within the VA compared to private sector
hospitals. Men with newly diagnosed prostate cancer will be identified
through the VA Registry. Cases will be selected on the basis of age at
diagnosis (40-64 years/65-74 years) and race (white and black). Within
the V.A., controls will be frequency-matched to the cases on the basis
of age and race. It is hypothesized that both genetic and environmental
factors contribute to the racial differential in both incidence and mortality
of prostate cancer among blacks and whites. This study will answer important
questions pertaining in black and white men concentrating on environmental
factors that impact on risk. Dietary intake and occupational exposures
such as agent orange, pesticides and other chemicals will be examined in
cases and controls. Levels of chlorinated pesticides and PCBs will be compared
in sera of a subset of cases and controls. Familial aggregation of prostate
cancer will also be studied. DNA form this same subset will be used to
generate further research. Additionally, we will explore issues related
to detection and treatment of prostate cancer in both blacks and whites
and between men enrolled in the VA versus private sector health car. We
hypothesize that racial differences in the incidence and mortality of prostate
cancer may be a result of multiple factors including those that are socioeconomic,
environmental, dietary and genetic. This research will provide insight
into gene-environmental interactions that initiate and promote prostatic
neoplasia as well as address whether there are differences in patterns
of care which impact morbidity and survival. Progress Report: As of November
1998, we have not accrued any patients into this study. We will be sending
out the first letters to potential recruits in December 1998.
DORGAN J. PREDIAGNOSTIC BREAST CANCER SERUM BANK. Crisp Data Base National
Institutes Of Health. Author Address: NCI, NIH
The objective of this serum bank is to provide a mechanism for prospectively
evaluating relations of serum concentrations of various analytes such as
hormones, antioxidant micronutrients, vitamin D, and environmental pollutants
with breast cancer risk. Background: The serum bank was created as part
of NCI's Biological Markers Project. Between 1977 and 1987, a total of
7,355 women free of breast cancer donated blood to the bank, and by the
end of followup in 1989, 146 of these women had been diagnosed with breast
cancer. Questionnaires that ascertained information on age, height, weight,
reproductive history, medical history, medications (including exogenous
estrogens), and family history of breast cancer were completed at each
blood collection. Serum has been stored at -70 degree C since it was collected.
Methods: The serum bank has been used for nested case-control studies of
breast cancer in relation to sex hormones, antioxidant micronutrients,
pesticides, and PCBs. Progress: We reported strong positive associations
of bioavailable estradiol and testosterone with postmenopausal breast cancer
in these women; those in the highest quartiles for these hormones were
at 5- and 6-fold excess risks, respectively. Laboratory assays of antioxidants,
pesticides, and PCB's have been completed and data analysis is underway.
Additional sex hormones, IGF-1, c-peptide, and vitamin D currently are
being measured, and estrogen, progesterone, and androgen receptor content
of tumors is being determined.
Studies Without Abstracts
Adami H-O, Bergstrom R, Mohner M, et al. Testicular Cancer in Nine Northern
European Countries, Int J Cancer, 59: 33-38, 1994
COWELL S, PORTIGAL C, NELSON CC, RENNIE PS, GLICKMAN BW. ANDROGEN- AND
GLUCOCORTICOID-LIKE ACTIVITY IN P-NONYLPHENOL AND PCBS. Source: 1999 ENVIRONMENTAL
MUTAGEN SOCIETY MEETING, WASHINGTON, D.C., USA, MARCH 27-APRIL 1, 1999.
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS; 33 (SUPPL. 33). 1999. 20.
GLATT H, SEIDEL A, BOCHNITSCHEK W, MARQUARDT H, MARQUARDT H, HODGSON
RM, GROVER PL, OESCH F. MUTAGENIC AND CELL-TRANSFORMING ACTIVITIES OF TRIOL-EPOXIDES
AS COMPARED TO OTHER CHRYSENE METABOLITES. Source: CANCER RES 46:4556-4565,1986
Prostate fibroblasts were cultured. PCBs were used to induce enzymes
to test mutagenicity.
Khudoleãi VV, Mizgirev IV, Maãiorova IG. Enzymatic imprinting
and its possible significance in carcinogenesis. Source: Vopr Onkol 1990;36(9):1045-52
MCQUAID S, O'BRIEN A, BUTLER MR, HUMPHRIES P. TRANSCRIPTIONAL
ACTIVATION OF THE GLUTATHIONE S-TRANSFERASE PI GENE IN HUMAN URETERIC AND
BLADDER CARCINOMAS. Source: CANCER LETT; 39 (2). 1988. 209-216. Keywords
include: CARCINOMA PROSTATE
Ross JS. Development of an Assay for Prostate Cancer Based on Methylation
Status of Glutathione S-Transferase (p). Govt Reports Announcements &
Index (GRA&I), Issue 25, 2001. Final rept. 1 MAr 1999-28 Feb 2001.
Author Address: Albany Medical Coll., NY.
Sakr WA, Haas GP, Cassin BF, et al. The Frequency of Carcinoma and Intraepithelial
Neoplasia of the Prostate in Young Male Patients, J Urology, 150:379-385,
1993
SINHA RP, PARULEKAR MR. EFFECT OF MAMMALIAN TISSUES ON MUTAGENICITY
OF SEVERAL N-NITROSO COMPOUNDS. Source: J FOOD PROTECTION 46:109-114,1983
Keywords include: prostate. (PCBs were used as an enzyme inducer
to test mutagenicity.)
SOEDERKVIST P, BUSK L, TOFTGAERD R, GUSTAFSSON JA. METABOLIC ACTIVATION
OF MUTAGENS AND ENZYMATIC ACTIVITIES IN THE RAT VENTRAL PROSTATE.
Source: ACTA PHARMACOL TOXICOL 49(SUPPL 1):47,1981
WARREN RJ, KIRKPATRICK RL, VOGELSANG RW. EFFECTS OF MIREX
AND A POLY CHLORINATED BI PHENYL ON PENTO BARBITAL INDUCED SLEEPING TIMES
AND ORGAN WEIGHTS OF MALE COTTONTAIL RABBITS. Source: VA J SCI; 26
(2). 1975 60. Keywords include: prostate
YUSPA SH, SHIELDS PG. ETIOLOGY OF CANCER CHEMICAL FACTORS.
Source: DE VITA, V. T. JR., S. HELLMAN AND S. A. ROSENBERG (ED.). CANCER:
PRINCIPLES AND PRACTICE OF ONCOLOGY, 5TH EDITION, VOLS. 1 AND 2. LXIX+1539P.(VOL.
1); LI+1585P.(VOL. 2) LIPPINCOTT-RAVEN PUBLISHERS: PHILADELPHIA, PENNSYLVANIA,
USA. ISBN 0-397-51574-X(SET); ISBN 0-397-51575-8(VOL. 1); ISBN 0-397-51576-6(VOL.
2).; 0 (0). 1997. 185-202. Keywords include: Prostate Cancer
and Polychlorinated biphenyl
Additional Prostate Cancer sections:
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