 |
Studies of Kidney Cancer and
PCBs
The following 29 studies show the possibility
that PCBs increase kidney and urothelial cancer risks. This may not
be a complete list of all kidney cancer research related to PCBs. For more,
visit the TOXNET database operated
by the National Library of Medicine (the source of these abstracts).
Keep in mind that these kidney cancer 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
-
PCB exposure produced a consistent increase in
kidney cancer
A review by researchers from the National Institute
for Environmental Health Sciences used an analysis of combined occupational
studies, and concluded that PCB exposure produced a “consistent increase
in kidney cancer,” although the actual number of cases was small.
(Longnecker et al, 1997)
Study #2
-
higher numbers of kidney cancer for men followed
PCB exposure
In January 1985, following a period of high electricity
demand, an electric transformer located in a residential building basement
and containing PCBs exploded in Reims. This led to the dispersion into
the building of polychlorobiphenyls (PCBs) and trichlorobenzene from the
inside of the transformer and the dispersion of PCB thermic breakdown products,
especially furans (PCDFs) and dioxins (PCDDs). 343 people were exposed
: firemen, EDF (French government-owned power company) workers, residents
of the building and visitors. A medical follow-up was organised until 1990
when it was suspended due to a poor participation. However, it had to resume
in 1994, due to health problems observed in personnel who had intervened
during the accident. The RNSP (Public Health National Network) was commissioned
by the Ministry of Health to make an epidemiological survey. Among the
most frequently reported symptoms within the highly exposed group of people
(75 people), important losses of memories, fatigue, itches and skin allergies
have been noted. The study of cancer incidence revealed higher numbers
of breast cancer for women, kidney cancer for men. This accident
led the French government to strengthen the existing legislation on PCBs:
1975: An order on behalf of the Public Health Code restricted the use of
PCBs and rendered their disposal mandatory after use. 1983: An order
on behalf of the Labour Code relating to labelling and packaging for hazardous
substances was issued. PCBs were classified as noxious substances. 1985:
Total ban on further installation and use of equipment containing PCBs.
1987: Mandatory disposal of all equipment containing more than 100ppm.
Despite this, the 96/99/CE European Directive relating to PCBs and PCTs
disposal has only been made French law in January 2001, and only after
France has been rebukby the European Commission for not respecting deadlines
set for the inventory phase for contaminated equipment and failing to present
a disposal scheme. (Cordier et al, 1996)
Study #3
-
machining fluids [including PCB-containing pyranol]
were associated with kidney cancer
A case/control study was carried out of cancer associated
mortality at a transformer assembly factory in Massachusetts. Seven types
of exposure with mutagenic or carcinogenic potential were rated together
with the operations in which they were used. The chemicals were pyranol
(1336363), benzene (71432), trichloroethylene (79016) (TCE), mixed solvents,
machining fluids, asbestos (1332214), and synthetic resins. The cohort
consisted of 1,821 white male subjects with 51,063 person years of employment.
Site specific cancer deaths were regarded as cases, and comparisons were
selected from deaths considered unassociated with any of the exposures.
Odds ratios (ORs) were calculated. Results showed that 28 exposure/cancer
associations could be identified as important in the binary exposure regressions
or in the contingency table screening. Pyranol lymphomas and solvent oral/laryngeal/pharyngeal
cancers showed a greatly reduced association, whereas a consistent positive
association was evident between benzene and brain tumors, other solvents
and lymphomas, and resins with lung cancer. Regressions with multiple exposures
were also computed. A modification of the induction latency analysis method
was used, and the only notable finding was an association between machining
fluids and kidney cancer. Associations of resins with rectal and lung cancer,
machining fluids with kidney cancer, and TCE with leukemias seemed to be
largely or entirely concentrated to post 1950 exposures. Cross tabulation
showed a similar association between level 2 solvents and reticulosarcoma.
The authors conclude that the link between machining fluids and kidney
cancer is new, and that this as well as a possible association between
lung cancer and resin systems deserve further investigation. (Greenland
et al, 1994)
Study #4
-
kidney cancer was reported in three utility workers
exposed to PCBs
Primary unifocal renal adenocarcinoma was reported
in three caucasian male utility workers exposed to polychlorinated-biphenyls
(PCBs). The first was 34 years old with a 5 year history of extensive unprotected
PCB contact as a painter in a transformer repair shop. The second was 43
years old, with a 14 year history of exposure to PCB oil as a linesman,
and the third was 56 years old, with 8 years work history as a painter
in a transformer repair shop. None of the cases reported any personal risk
factors, although they had histories of occupational exposures to organic
solvents, herbicides, electromagnetic fields and PCBs. Pathological examination
of the tumors showed solid cell sheets with eosinophilic cytoplasm and
some cuboidal cells (first case), solid cell sheets with mostly clear cytoplasm
and a prominent vascular component (second case); and clear cells in sheets
as well as tubular and alveolar structures, accompanied by a moderately
dense inflammatory infiltrate (third case). Traces of herbicides and pesticides
and their products, but no PCBs, were found in sera of the first two cases.
The second case reported a chloracne like rash. The authors conclude that
electrical utility workers are exposed to a variety of chemical and physical
agents, and recommend an epidemiological investigation of renal adenocarcinoma
in this industry. (Shalat et al, 1989)
Study #5
-
deaths caused by kidney cancer increased significantly
with increasing exposure to pentachlorophenol [contaminated with dioxin
--- certain PCBs are dioxin-like]
The cancer risks associated with pentachlorophenol
(87865) (PCP) exposure were examined. Work history records were used to
form the study cohort of 770 employees of Dow Chemical Company in Michigan.
Industrial hygiene and process data were used to evaluate PCP exposure.
A modified life table approach allowed for the estimation of expected deaths
and the calculation of standardized mortality ratios (SMRs). While 242.5
total deaths and 52.6 deaths caused by malignant neoplasm were expected,
observed deaths totaled 229 and 50, respectively. A significant excess
of deaths caused by gastric or duodenal ulcer was observed, with an SMR
of 357. The prevalences of death caused by kidney cancer, gastric and duodenal
ulcer, cirrhosis of the liver, and all accidents increased significantly
with increasing exposure. Although the excess in lymphopoietic cancer deaths
was not significant, a trend toward higher risk with higher PCP exposure
was evident. However, a significant number of deaths was observed in the
low exposure group, as well as in the groups exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin
(1746016) and other benzodioxins. The authors conclude that this study
does not support the possibility that PCP exposure increases the risk of
liver and adrenal gland cancers. Workers may have incurred an increased
risk of death due to some specific causes, but may have been associated
with some factor other than PCP exposure. (Ramlow, 1996)
Study #6
-
PCBs demonstrate increased risk of urothelial
cancers [ includes kidney cancers]
Classification of workers' exposure status by combinations
of occupational title and industrial category, or job/exposure matrix,
was used on census data to identify chemicals carcinogenic to the lower
urinary tract. Fifty chemical compounds were chosen on the basis of prior
identification as definite or probable urinary tract carcinogens. The exposed
group was chosen from occupations in which at least 10 percent of persons
in the job category had estimated exposures during the census year of at
least 1 hour per week to any of the selected compounds. Those in the remaining
occupational groups were assigned to the unexposed group. Links between
exposures and work tasks were constructed, and the positive predictive
values for each link were characterized. Analysis was restricted to the
1,905,660 employed males aged 20 to 64 years as of 1960; the observation
period was from 1961 to 1979. Cases of urothelial cancer were identified
through the Swedish Cancer Registry. A total of 556,429 were assigned to
the exposed group. Exposure to creosote (8001589), chlorinated phenols,
and phenol (108952) judged as low to moderate in predictive value was found
to increase the risk of bladder cancer (relative risk (RR) 1.8) and renal
pelvic cancer (RR 2.6). Exposure to some lubricating oils and fluids caused
slight increase in the RR. Chemical process workers with exposures to unspecified
aromatic amines were showed to be at increased risk of bladder cancer.
Exposure to polycyclic aromatic hydrocarbons caused increases in the RR,
dependent upon the source of combustion gases. Other substances demonstrating
increased risk of urothelial cancers were chlorinated aliphatic hydrocarbons
and polychlorinated biphenyls. (Steineck et al, 1989)
Study #7
-
PCB pretreatment increased the protein binding
of another kidney toxicant and carcinogen (Tris-BP)
The nephrotoxicant and nephrocarcinogen tris(2,3-dibromopropyl)phosphate
(Tris-BP) is activated to products which bind covalently to microsomal
protein by a cytochrome P-450 dependent oxidation reaction. Binding to
rat liver microsomes proceeds 15 times faster than with kidney microsomes.
The binding in liver microsomes is markedly increased by phenobarbital
pretreatment, the apparent Vmax of the reaction is 175 pmol/mg microsomal
protein/min with control microsomes and 1053 pmol/mg protein/min with induced
microsomes. Binding with kidney microsomes is doubled after pretreatment
with polychlorinated biphenyls. 2,3-Dibromopropanol (2,3-DBP), a hydrolysis
product of Tris-BP, is also activated to covalently protein-bound products,
but at a much slower rate than Tris-BP. Administration of Tris-BP to rats
leads to its covalent binding to proteins in liver and kidney, with 5 times
higher binding levels in kidney than in liver, correlating with its relative
organotoxic potential in single dose experiments. Binding to proteins in
the kidney was increased by pretreatment of animals with polychlorinated
biphenyls. A covalent interaction of Tris-BP with DNA could be demonstrated
when DNA was added to liver microsomal incubations in vitro and to DNA
extracted from liver and kidney after administration of Tris-BP in vivo.
The binding levels were 4 times higher to kidney DNA than to liver DNA.
(Soderlund, et al, 1981)
Study #8
-
PCBs promoted the production of nodules
-
adenocarcinomas of kidney were composed of clear
cells arranged in solid, alveolar patterns
The effects of polychlorinated biphenyls (PCBs) and
phenobarbital (50066) (PB) on the induction of liver and kidney tumors
by dimethylnitrosamine (62759) (DMN) were investigated in rats. Male Fischer-344-rats
were maintained on a diet containing 0.04 percent DMN, 500 parts per million
(ppm) PCB, or 500 ppm PB. Rats were divided into 11 groups, each group
containing 20 animals. Group 1 was given a DMN containing diet for 2 weeks,
a basal diet for 2 weeks and a PCB diet for 28 weeks. At week 5, animals
underwent unilateral nephrectomy (UN). Group 2 was given DMN and PCB diets
without UN; group 3 was given PCB plus UN; group 4 was given PCB alone;
group 5 was given DMN and PB with UN; group 6 was given DMN and PB; group
7 was given PB plus UN; group 8 was given PB alone; group 9 was given DMN
plus UN; group 10 was given DMN alone; and group 11 was given the basal
diet. All animals were sacrificed at week 32 and complete autopsy was performed.
Rats fed DMN and PCB showed decreased weight gain; the group given DMN
plus PB lost weight during the treatment. In the rats fed DMN and PCB,
with or without UN, the liver was modular with tan nodules. In the kidneys
of rats fed DMN alone, grey nodules were also observed. Histopathological
findings included rounded hyperplastic nodules with compression of normal
liver tissue and constituent hepatocytes were larger than normal. Hepatocellular
carcinoma demonstrated irregular trabecular arrangement of hepatocytes
and was indicated by nuclear hyperchromatin and increased mitotic index.
Cholangiofibrosis demonstrated severe bile duct proliferation with prominent
fibrosis. Adenocarcinomas of kidney were composed of clear cells arranged
in solid, alveolar patterns. The authors conclude that PCBs and PB promote
the production of nodules and hepatocellular carcinomas in rats pretreated
with DMN. (Arai et al, 1983)
Study #9
-
urothelial cancer [including kidney cancer] relative
risks for PCB exposures were 3.6, after adjusting for year of birth and
smoking
A case control study of the association between exposure
to benzene (71432), exhausts, and other industry related chemicals and
the risk of urothelial cancer was conducted. The cohort consisted of 320
cases of urothelial cancer occurring in males living in Stockholm, Sweden
between 15 September 1985 and 30 November 1987 who were born between 1911
and 1945. The referents consisted of 363 randomly selected residents of
Stockholm. The subjects were interviewed by questionnaire to obtain information
on exposures, occupational history, and smoking and dietary habits. Detailed
information was sought on exposure to benzene, combustion gases from coal,
gasoline, and other products, cutting fluids, asbestos (1332214), aromatic
amines, polychlorinated biphenyls (PCBs), and other chlorinated organic
compounds. Two cases reported significant exposure to aromatic amines;
they were omitted from further analysis. The urothelial cancer relative
risk (RR) for current and former smokers was 3.5 and 2.0, respectively.
Crude RRs for exposure to benzene and PCBs were 1.9 and 2.9, respectively.
After adjusting for year of birth and smoking, the RRs for benzene and
PCB exposures were 2.0 and 3.6, respectively. The risk due to benzene exposure
increased with increasing estimated dose for subjects who had been exposed
for at least 20 years before the study. Cases who had moderate or high
annual exposures to gasoline and diesel exhausts had an RR of 7.1. After
controlling for any annual exposure to benzene the RR was reduced to 5.1.
Current smokers exposed to benzene had an RR of 7.5. Subjects exposed to
benzene who also had high dietary intakes of fried foods and fat had RRs
of 9.3 and 10.7, respectively. Subjects exposed to benzene who were not
taking vitamin-A supplements had an RR of 5.8 compared to those taking
vitamin-A. When categorized by occupation and industry, the highest risk
was associated with employment in the rubber industry. The authors conclude
that exposure to benzene is associated with an increased risk of urothelial
cancer. The risk depends on mean annual dose and exposure has to start
at least two decades before the observation period. (Steineck et
al, 1990a)
Study #10
-
for PCBs and urothelial cancers, data are scarce
(prior to 1990)
In a previous cohort study by our group, certain
industry-related chemicals were judged as warranting further attention
as possible urothelial carcinogens. In this paper, the epidemiologic literature
of cancer of the lower urinary tract is evaluated for these substances.
We would like to add combustion gas/soot from coal to the substances considered
as increasing the risk urothelial cancer. It is, however, uncertain whether
this risk is due to contaminants of aromatic amines in tar volatiles or
whether it depends on other agents, such as nitroarenes or polycyclic aromatic
hydrocarbons. Furthermore, we find some support for the hypothesis that
exposure to chlorinated aliphatic hydrocarbons increases the risk of urothelial
cancer. For creosote, cutting fluids and cutting oils, hair dyes, and polychlorinated
biphenyls, data are scarce. Available data do not support the hypothesis
that asbestos is associated with urothelial cancer. "Publication bias"
such that only limited (Steineck et al, 1990b)
Study #11
-
one cohort study gave some support for PCBs being
associated with urothelial cancer
The purpose of this thesis was to identify the risk
factors for urothelial cancer. Two cohorts were followed up and a case-referent
study was made in the county of Stockholm in 1985-87. Pipe smoking increased
and intake of supplements (mainly containing vitamin A) decreased the risks.
The hypothesis that intake of browned material formed during cooking is
an important risk factor was supported in a case-referent study. A dose-response
relationship was also seen with an increasing average daily intake of fat.
One cohort study gave some support for combustion gases from coal, creosote
and polychlorinated biphenyls being associated with urothelial cancer.
In the case-referent study, benzene was identified as a possible risk factor.
In the epidemiological literature, among industry-related chemicals, only
certain combustion gases from coal, besides aromatic amines, have convincingly
been linked to urothelial cancer. (Steineck, 1990c)
Study #12
-
PCBs increased risk of urothelial cancer
We have previously reported a study in which a job-exposure
matrix was applied to census data, identifying, e.g., polychlorinated biphenyls
(PCBs) and creosote as increasing the risk of urothelial cancer. In this
article, we expand on some theoretical issues, and present detailed accounts
of constructed linkages for PCBs, creosote, and phenols. For agents of
interest, one should emphasize the positive predictive value rather than
the sensitivity in the construction of the matrix. The reverse is true
for confounding factors; to avoid residual confounding after restriction
to subjects unexposed for the confounding factors, one should emphasize
sensitivity, possibly compromising the positive predictive value. This
discrepancy between agents of interest and confounding factors may limit
the application of a general matrix for studying several different diseases.
The construction of the matrix is much harder, if sensitivity rather than
positive predictive value is emphasized for an agent. Confounding from
industry-related agents arises due to a true mixed exposure in certain
work tasks, but also due to a gross classification of occupations in the
census. One should not confuse different levels of the positive predictive
value with exposure dose. A "dose-response" with different levels of positive
predictive value reflects an accuracy of the matrix, not a biological phenomenon.
Studies with exposure information from a job-exposure matrix applied to
registers with scant information on occupation and industry may be warranted
for exposures and diseases for which previous studies with a detailed documentation
of exposure have low precision. (Plato et al, 1993)
Study #13
-
PCBs altered kidneys’ histopathology
-
PCB congener 118 accumulated in kidneys
A study was conducted on the toxic effects of 3,3',4,4'-tetrachlorobiphenyl
(32598133) (PCB-77) and 2,3',4,4',5-pentachlorobiphenyl (32598144) (PCB-118)
following dietary exposure. The effects of PCB-77 and PCB-118 on various
biological parameters were assessed following treatment of Sprague-Dawley-rats
with up to 10,000 parts per billion (ppb) PCB-77 or PCB-118 for 13 weeks.
No clinical evidence of toxicity was observed. Increases in the absolute
and relative spleen weights of male rats treated with 1,000 or 10,000ppb
PCB-77 were noted. Treatment related biochemical changes included increases
in the activity of hepatic microsomal ethoxyresorufin-O-deethylase in animals
treated with the highest doses of PCB-77 or PCB-118. A significant decrease
in the liver vitamin-A content was seen as well in animals treated with
the highest dose of PCB-77. An increase in the concentration of 3,4-dihydroxyphenylacetic-acid
was seen in the brains of males exposed to the highest dose of PCB-77 while
females treated with 2,000ppb PCB-118 exhibited significant decreases in
levels of dopamine and homovanillic-acid in selected areas of the brain.
Histopathologic treatment related alterations were identified in the livers,
thyroid glands, spleens, kidneys, and bone marrow of both PCB-77 and PCB-118
treated animals. A dose dependent accumulation of PCB-118 was noted in
the fat and liver of treated animals with lower levels identified in the
kidneys, brains, and hearts. In contrast, measurable PCB-77 levels were
detected only in the fat and liver of the highest dose animals. Based on
these data the no observed adverse effect level for PCB-77 was calculated
to be 100ppb in the diet or 8.7 micrograms/kilogram body weight per day
while that for PCB-118 was 200ppb in the diet or 17 micrograms/kilogram
body weight per day. (Chu et al, 1995)
Study #14
-
PCBs had physiological effects on kidney function
-
long-term cancer risks (beyond 8 years) were not
followed
In response to a request from the Indiana State Board
of Health, a follow up study was conducted of workers occupationally exposed
to polychlorinated-biphenyls (1336363) (PCBs) at the Westinghouse Electric
Corporation's Transmission and Distribution Components Division (SIC-3629),
Bloomington, Indiana. A cross sectional study had been conducted in 1977.
Workers in the high and low serum PCB groups from that study were invited
to participate; 60 of 66 workers originally studied participated in this
study. Those in the high level group were on the average 5.6 years older
than the low PCB group. Use of PCBs was discontinued in 1977. By 1985 the
levels of serum PCB concentrations in the low group had decreased by an
average of 85% of the 1977 value. Levels in the high PCB group had decreased
by an average of 90%. No clinical abnormalities attributable to PCB exposure
were noted. Serum PCB levels were positively and significantly correlated
with triglycerides, cholesterol, total bilirubin, conjugated bilirubin,
beta-glucuronidase, 5'-nucleotidase, serum apolipoprotein-Al, serum apolipoprotein-B,
urinary creatinine, and urinary alanine-aminopeptidase. According to the
authors, the biochemical findings are indicative of the physiological effects
of PCBs on lipid metabolism, liver function and kidney function. The clinical
significance of these findings 8 years after occupational exposures had
ceased is unknown. (Steele et al, 1990)
Study #15
-
PCB-induced enzymes were highest in the kidney
and liver
-
this pattern was in accord with observations in
other species
The summer flounder, Paralichthys dentatus, is a
commercially important species of flatfish found on the East Coast of the
United States, from Cape Hatteras to Maine. Pelagic, stomachless larvae
metamorphose into the benthic, gastric, juvenile flatfish in shallow coastal
bays, lagoons and estuaries during the spring. In summer flounder, metamorphosis
is regulated by thyroid hormones (TH), and chemically induced hypothyroidism
inhibits metamorphosis past the very early stages. PCBs are among the major
pollutants found in industrially impacted coastal ecosystems, and are known
to act as endocrine disrupters by lowering blood TH levels in mammals and
some fish. This project is concerned with determining the developmental
effects of the dioxin-like CB 126 on metamorphosing larvae, and ultimately
to understand if any of the effects are mediated by thyroidal disruption.
Here we present results of the first experiments carried out 30-day-old
(premetamorphic) and 39-day-old, (early metamorphosing) larvae to establish
their sensitivity to CB 126. Larvae were exposed to radiolabeled CB 126
through the water, and grown out for 3 weeks to assess mortality. Cytochrome
P4501A1 immunoreactivity was measured as a marker of Aryl hydrocarbon Receptor
pathway activation in liver, small intestine, stomach, and kidney. Mean
metamorphic stage was calculated at the end of growout to determine if
sublethal doses had an effect on metamorphosis. The younger group appeared
more sensitive than the older (LD 20 = 20.9 pg/mg and 170 pg/mg, respectively).
Sensitivity to CB 126 was similar to that observed in embryos of other
marine fish (e.g. Fundulus heteroclitus). CYP1A1 induction was highest
in the kidney and liver, lowest in anterior intestine, and was maximal
near the LD 20 in all tissues; this pattern was in accord with observations
in other species. In the younger group we observed a dose-dependent trend
toward more advanced metamorphic stage, suggestive of an effect of CB 126
on developmental rate. (Soffientino et al, 2002)
Study #16
-
PCB mixture Aroclor 1248 caused loss of kidney
cell viability and cell death in a concentration- and time-dependent manner
-
individual PCB congeners produced kidney cell
death by different mechanisms
The effects of a commercial polychlorinated biphenyl
(PCB) mixture (Aroclor 1248) and two individual PCB congeners were evaluated
on rat renal proximal tubule culture cell viability and internucleosomal
DNA fragmentation (DNA ladder) characteristic of apoptosis. Treatment with
Aroclor 1248 caused the loss of cell viability and promoted apoptosis in
a concentration- and time-dependent manner. The two PCB congeners assessed
can also induce apoptosis. However, the extent of apoptosis generated was
greater for the non-ortho-substituted planar congener (3,3',4,4-tetrachlorobiphenyl)
than for the di-ortho-substituted nonplanar congener (2,2',4,4',5,5'-hexachlorobiphenyl).
This correlated with the loss of cell viability since the planar compound
is much more cytotoxic. The results suggest a different molecular mechanism
in the induction of apoptosis by planar or nonplanar PCB congeners.
(Perez-Reyes, et al, 2001)
Study #17
-
PCBs were associated with abnormal cellular changes
in the renal corpuscle (kidneys)
The purpose of this study was to evaluate the potential
toxic effects of chronic sublethal polychlorinated biphenyl (PCB) exposure
on feral fish, using histopathology as an endpoint. Histopathological study
of bream (Abramis brama) and asp (Aspius aspius) living in a PCB-polluted
freshwater lake revealed abnormal cellular changes in the renal corpuscle
of both species. Dilation of glomerular capillaries (DGC), mesangial edema
(ME), an adhesion between visceral and parietal layers of Bowman's capsule
(ABC), and filling of Bowman's space (FBS), were highly prevalent features
in lake fish. The prevalence of each of these lesions was significantly
lower, or totally absent in fish caught from reference locations. Cellular
alterations in liver, gill, gonads, spleen, and intestine were all linked
to seasonal changes. The results suggest that some of the observed histopathological
changes in renal glomeruli, particularly DGC and ME, could possibly indicate
a prolonged chemical stress caused by PCBs and related compounds. It is
also possible that chronic PCB exposure may have suppressed and weakened
the immuno systems of exposed fish making them more vulnerable to secondary
parasitic infections. (Koponen et al, 2001)
Study #18
-
PCBs increased the kidney dysfunctions caused
by trichloroethylene exposure
Several polyhalogenated biphenyls are known to be
ubiquitous environmental contaminants. Male ICR mice were fed a control
diet or the same diet supplemented with 100 ppm polybrominated biphenyl
(PBB) or 200 ppm polychlorinated biphenyl (PCB) for 28 days before single
i.p. injections of various quantities of trichloroethylene (TRI), tetrachloroethylene
(TET), 1,1,2-trichloroethane (TCE), or carbon tetrachloride (CCl4). The
ratio of liver weight to body weight was increased by dietary PBB and dietary
PCB. PBB appeared to be more potent in this respect. Functional damage
to the liver (elevated serum glutamic oxaloacetic transaminase activity)
was not produced by acute administration of TRI, TET or TCE. CCl4-induced
liver damage was greater in PCB-treated mice than in controls, and greater
in PBB-treated than in PCB-treated mice. Functional renal damage (elevated
blood urea nitrogen concentration, decreased organic anion transport capacity)
was produced by acute administration of all solvents except TET. TRI-induced
renal dysfunction was potentiated by dietary PBB and dietary PCB. Both
TCE-induced and CCl4-induced renal dysfunction were potentiated by dietary
PBB but not by PCB. Mice fed a diet containing 0, 20 or 100 ppm PBB for
20 days were subsequently injected with various doses of CCl4 and 96 h
LD50 values were determined. The LD50 CCl4 was lower in mice treated with
20 ppm PBB than in control mice and lower in mice treated with 100 ppm
PBB than in those treated with 20 ppm PBB. (Kluwe et al, 1979)
Study #19
-
low amounts of PCBs were enough to modify kidney
cell membrane fluidity
The influence of different polychlorinated biphenyls
(PCBs) upon dynamic properties of membranes from rat renal tubular cell
cultures has been investigated. Studies have been realized with Aroclor
1248 (a commercial PCB mixture with 48% chlorine by weight), and two pure
PCB congeners: 3,3',4,4'-tetrachlorobyphenyl (a coplanar compound) and
2,2',4,4',5,5'-hexachlorobiphenyl (an ortho-substituted nonplanar congener).
Changes in the membrane fluidity were measured by the fluorescence polarization
technique using the probe diphenylhexatriene. The treatment of cells with
Aroclor 1248 increased membrane fluidity in a dose-dependent manner. Even
though rat renal tubular cell cultures accumulated only a low amount of
PCBs when cells were incubated in presence of the toxicant, that small
quantity was enough to modify the membrane fluidity. Interestingly, a significant
increase of membrane fluidity was found in presence of 2,2',4,4',5,5'-hexachlorobiphenyl,
but no significant dif [incomplete abstract] (Lopez-Aparicio, et
al, 1997)
Study #20
-
kidney damage is one of the main PCB effects in
birds
The current knowledge about polychlorinated biphenyls
(PCBs) including the toxicology of these compounds as well as the levels
of PCBs found in nature is summarized and evaluated. A number of studies
including acute single dose, acute feeding and sublethal dose experiments
are cited. A fair amount of information has been collected about PCBs but
the toxicology of these compounds is poorly known in comparison to that
of chlorinated pesticides. No definite work has been done to establish
LD50 values for the various formulations of PCBs. The most important effects
of the PCBs are their long-range sublethal effects. The most common ones
in the rat, guinea pig and rabbit as well as in the chicken and Bengalese
finch are summarized. PCBs mainly cause pathological changes in the liver
of guinea pigs, rats and rabbits. The changes include moderate atrophy,
necrosis and weight increase. The main effect of PCBs in birds are increased
fluid in the pericardial sac, renal damage and reduction in size and/or
atrophy of the spleen. PCB residues have been found in wild life from Great
Britain, Sweden, Canada, Germany, the Netherlands and from the United States.
Like DDT, PCBs are capable of accumulating as they advance up the food
chain. Recent studies by Risebrough et al. (1968 and 1970) show that twice
as much PCB as DDT has been found in the tissues of some seabirds in San
Francisco Bay. Evaluation of the available data on PCBs in tissues tends
to parallel that of DDE, at least in industrial areas. The DDE rate is
lowest near industrial areas, indicating that PCBs are not carried quite
as readily to remote areas. More research is needed to ascertain the presence
of PCBs in higher forms of life and the effects of this presence. Finding
the major source(s) of PCBs entering the environment is the most critical
area for research. Once the leak is found, strong legislative control should
be enacted to stop it.
Study #21
-
kidney enzyme activities were increased by PCBs
-
kidney toxicity of chloroform was reduced by PCBs
ICR mice were treated with phenobarbital (PB), 3-methylcholanthrene
(3MC), TCDD or PCB. Renal and hepatic microsomal enzyme activities were
increased by 3MC, TCDD and PCB. Hepatic, but not renal, microsomal enzyme
activities were increased by PB. Toxicity of chloroform to the liver was
increased by PB pretretment. Pretreatment with TCDD, however, decreased
hepatotoxicity of chloroform. No effect of chloroform toxicity to the liver
was noted by pretreatment with 3MC or PCB's. Renal toxicity of chloroform
was reduced by TCDD or PCB pretreatment, but no effect by PB was noted
on kidney damage caused by chloroform. These results suggest that the chloroform
metabolites ultimately responsible for renal and liver damage are not generated
at a common site. The metabolite probably responsible for liver damage
is apparently generated in the liver, and similarly, the one responsible
for kidney damage, in the kidney.
Study #22
-
certain PCBs decreased liver Vitamin-A content
60% within 7 days, and increased kidney Vitamin-A levels 3-fold
The kinetics of liver and kidney retinol and retinyl-palmitate
levels were examined following single intraperitoneal injections of DDT
(50293), 2,2',5,5'-tetrachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl (32598133),
or 2,2',4,4',5,5'-hexachlorobiphenyl (35065271) to male Sprague-Dawley
rats. The polychlorinated biphenyls (PCBs) were given in doses of 300 micromoles/kilogram
(micromol/kg), and DDT was a given at a dose of 150micromol/kg. Administration
of 3,3',4,4'-tetrachlorobiphenyl, but not the other PCBs, decreased total
liver vitamin-A content within 7 days of administration. This decrease
left vitamin-A levels of 40 percent of control animals. A three fold rise
in kidney vitamin-A, primarily retinol, accompanied he decrease in liver
vitamin-A. Even so, the rise in kidney vitamin-A was minimal compared to
its loss from the liver. The induction of various drug metabolizing enzymes
or retinyl-palmitate-hydrolase activity, a key enzyme in hepatic retinyl-palmitate
hydrolysis, was not implicated in the depletion of hepatic vitamin-A. It
is suggested that chemical or redox changes in the liver as a result of
the toxicity of the xenobiotic may result in the nonenzymatic destruction
of the liver vitamin-A stores.
Study #23
-
certain PCBs caused significant increases in kidney
retinol (Vitamin-A) content
Changes in vitamin-A parameters were compared with
the kinetics of induction of various drug metabolizing enzyme activities
using 1,1,1-trichloro-2,2-bis-(4-chlorophenyl)ethane (50293) (DDT) and
several prototypic polychlorinated biphenyls (PCBs). Weanling male Sprague-Dawley-rats
were given a single intraperitoneal injection of a synthetic PCB at 300
micromoles/kilogram (micromol/kg) or DDT at 150micromol/kg. Rats were sacrificed
1, 3, 5, or 7 days thereafter. PCBs used included 2,2',5,5'-tetrachlorobiphenyl
(2,5-PCB), 3,3',4,4'-tetrachlorobiphenyl (32598133) (3,4-PCB), or 2,2',4,4',5,5'-hexachlorobiphenyl
(35065271) (2,4,5-PCB). Only rats treated with 3,4-PCB showed a significant
decrease in whole liver vitamin-A content during the first week following
treatment. A significant increase was noted in kidney retinol content.
Only 2,5-PCB and 3,4-PCB altered serum retinol levels, with decreases on
days 1, 3, and 5 following treatment. DDT and 2,4,5-PCB increased cytochrome-P-450
content and the activities of aminopyrine-N-demethylase and aldrin-epoxidase
in liver. No change was noted in any vitamin-A parameter in DDT or 2,4,5-PCB
exposed livers. Only marginal changes in drug metabolizing enzyme activities
were induced by 2,5-PCB. 3,4-PCB was a potent inducer of cytochrome--P-450
dependent benzo(a)pyrene-hydroxylase, aryl-hydrocarbon-hydroxylase, and
uridine-diphosphate-glucuronosyltransferase activity. Treatment with 3,4-PCB
also decreased liver total vitamin-A content and levels of serum retinol
and caused a significant increase in kidney retinol. No highly significant
correlations were found among the vitamin-A levels and drug metabolizing
enzyme activities in the liver. (Azais et al, 1987)
Study #24
-
sulfur-containing PCB metabolites accumulate in
the kidney
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 #25
-
PCBs increase the protein synthesizing activity
of kidney pH 5 supernatant fractions
Homogenates of liver and of kidney cortex were obtained
from control rats and from rats treated with the polychlorinated biphenyls
(PCBs) Aroclor 1254, and were separated into ribosomes and into the postmicrosomal
supernatant fraction. The latter fraction from liver and kidney was used
to prepare the pH 5 supernatant fraction, containing elongation factors
1 and 2 (EF 1 and EF 2) for protein biosynthesis. These fractions were
incubated with KCl-washed ribosomes obtained from control rat liver. The
incorporation of (14C)phenylalanyl-tRNA into peptide was increased with
the liver and kidney preparations derived from the treated rats. The elongation
factor 1-dependent binding of (14C)phenylalanyl-tRNA to ribosomes was also
markedly increased both with the liver and the kidney preparations obtained
from the rats that had received PCBs. (Cappon et al, 1976)
Study #26
-
kidneys are more sensitive than lungs to PCB enzyme
induction
In this report, we have investigated the effect of
dietary exposure to Aroclor 1254 (1-100 ppm) given chronically or discontinuously
over an 84-day time interval to the female F344 rat. Cytochrome P4501A
was quantified in lung and kidney by measuring the dealkylation of ethoxyresorufin
substrate and by Western immunoblotting. P4501A displayed a dose- and time-dependent
increase in both extrahepatic organs. The kidney appeared to be more responsive
to induction than lung at all doses (maximum of 500-fold induction following
84 days exposure to 100 ppm). Further, there was evidence by enzymatic
activity, immunoblotting and Northern analysis of total RNA for the presence
of 1A2 in the most highly induced kidneys. The decline in 1A induction
observed following discontinuous exposure was more prominent in the kidney
than in the lung. These data demonstrate the sensitivity of kidney to P4501A
induction capacity as compared to lung, although the persistence of the
induction re [incomplete abstract) (Beebe, et al, 1995)
Study #27
-
PCB mixture Aroclor 1254 altered liver and lung
tissue more than kidney tissue
The effects of a tumor promoting polychlorinated
biphenyl mixture, Aroclor 1254, on I-compounds (tissue, species and sex
dependent DNA modifications that increase with age in untreated rodents)
were studied by 32P-postlabeling in male Sprague-Dawley rat liver, kidney,
and lung DNA. Aroclor 1254 was dissolved in corn oil and intraperitoneally
(i.p.) injected (2 X 500 mg/kg, 2 weeks apart) into 3-month-old rats. Control
rats were given corn oil. Groups of 3 animals were sacrificed at 2 and
6 weeks after the second injection of corn oil or Aroclor 1254. At both
time points Aroclor 1254-treated rats had significantly lower body weights
and higher liver weights while kidney and lung weights were unaffected.
Thymidine incorporation into liver and lung DNA was significantly increased
at both time points, while kidney DNA showed a small decrease at 2 weeks.
Treatment resulted in significant reductions (ranging from 29 to 100%)
of each of nine liver I-spots at 2 and 6 weeks. In treated rats there was
no decrease in kidney I-spots at 2 weeks, while the levels of only two
out of ten kidney spots were reduced by 42-91% at 6 weeks. At 2 weeks three
out of seven and at 6 weeks four out of seven lung I-spots were lowered
by 51-100% in the Aroclor 1254-treated rats. Thus the effects decreased
in the order liver > lung > kidney. Since Aroclor 1254 has been reported
to be a tumor promoter in liver and lung but not kidney, these results
suggest a correlation between organ specific promotion of carcinogenesis
by Aroclor 1254 and the reduction of DNA I-compounds. (Nath et al,
1991)
Study #28
-
PCBs promoted liver cancers, but not kidney cancers,
in rats treated with nitrosamines
The effects of phenobarbital (PB), polychlorinated
biphenyl (PCB) and sodium saccharin (SS) on hepatic and renal
carcinogenesis induced by N-ethyl-N-hydroxyethylnitrosamine (EHEN) were
examined in male F344 rats. The rats were given 0.1% EHEN in their drinking
water for 2 weeks and then diet containing 0.05% PB, 0.05% PCB or 5% SS
for 32 weeks. In week 3, the right kidney was removed to promote
renal neoplasia. The incidence of hepatocellular carcinoma was much higher
in rats given PB or PCB than in controls given EHEN alone. PB administration
significantly decreased the average number of renal-cell tumors per unit
area and SS reduced the numbers of early neoplastic nodules. Treatment
with PCB had no effect on renal carcinogenesis. These results
indicate that chemicals may have either a promotive or inhibitory effect
depending on the organ. (Hirose et al, 1981)
Study #29
-
incomplete abstract --- study may correlate PCBs
and kidney cancer
The validity of retrospective assessment of occupational
exposure greatly depends on the amount of detail in the available information,
on the knowledge of the specific industrial process by the experts, and
on the criteria adopted to define relevant exposure. These criteria are
difficult to standardize and are rarely made explicit in published reports,
which makes it difficult to interpret inconsistencies among different studies.
In two ongoing case-control studies on kidney cancer and, respectively,
malignant lymphomas, a detailed occupational history was obtained and supplemented
by 19 additional questionnaires, specifically addressing industrial activities
where the knowledge of job title alone would have been insufficient for
reliable exposure assessment. One further questionnaire was used to collect
details of task and environment for all the other activities. These data
are used to establish probability, intensity and frequency of exposure
to 30 substances known [incomplete abstract] (Belletti et al,
1993)
Upcoming Research
SINCLAIR JA. EFFECTS OF ARSENIC ON CYTOCHROME
P450 Source: Crisp Data Base National Institutes of Health.
Author Address: DARTMOUTH MEDICAL SCHOOL, HANOVER, NH 03755-3835
-
arsenic modulates the accumulation and elimination
of PCBs
-
arsenic is associated with kidney cancer
-
PCB accumulation may boost arsenic’s tendency
to produce kidney cancer
-
[Northeast Wisconsin has many areas of high arsenic
levels in drinking water]
Arsenic is found at high levels in almost half of
all Superfund sites as well as many public and private water supplies in
the northeastern and western regions of the United States. High levels
of arsenic in drinking water are associated with an increased risk of skin,
bladder, lung, and kidney cancer. Previous work in this and other laboratories
has demonstrated that arsenic can have substantial effects on specific
cytochrome P450s (CYPs) that are principally responsible for metabolism
of drugs and other xenobiotics by the liver, lung and other organs. In
particular, arsenic exposure decreases the induction of CYPs by chemicals
that are subsequently metabolized by these CYPs. We hypothesize that arsenic-induced
alterations in CYP mediated xenobiotic metabolism may have a significant
impact on the response of humans and other organisms to other toxic chemicals,
which might occur in Superfund sites containing arsenic in combination
with other metals and organic contaminants. This is postulated to increase
the bioaccumulation of other toxic chemicals, and therefore these effects
may contribute to arsenic- induced cancer and vascular disease and/or enhance
the toxicity of other chemicals. The overall goal of this project is to
determine the effects of arsenic (II I) and other selected metals on specific
liver CYPs. Our previous studies have demonstrated in hepatocytes in culture
that low concentrations of arsenic significantly decrease induction of
several major CYPs. These arsenic mediated decreases are not due to the
induction of heme oxygenase, depletion of heme, or oxidative damage as
had been previously postulated. We hypothesize that these effects occur
mainly at the post-transcriptional level. Our specific aims will be to:
1) determine in intact rodents the effects of acute and chronic exposure
to arsenic (III) on induction of CYPs, and the ability of arsenic to modulate
accumulation and elimination of polychlorinated biphenyls and drugs; and
2) determine, in cultured hepatocytes, the post-transcriptional mechanisms
by which arsenite specifically decreases synthesis of rat CYPA23 and chick
CYP2H1. These studies may provide insight into effects of arsenic and other
toxic metals, in combination with exposures to other toxic agents, that
have not previously been appreciated. Since most Superfund sites and other
waste sites contain complex mixtures of toxins, and over 60% of these sites
contain toxic metals, understanding their effects when present in combinations
will be important for our overall evaluation of the health effects of these
agents.
References Without Abstracts
REIF AE. THE CAUSES OF CANCER. WHILE
SOME CANCERS ARE GENETICALLY FATED TO APPEAR, MOST HAVE NOW BEEN TRACED
TO ENVIRONMENTAL FACTORS. Source: AM. SCI. 1981, 69() 437-447
STELLMAN S, STELLMAN J. HEALTH PROBLEMS
AMONG 535 VIETNAM VETERANS POTENTIALLY EXPOSED TO TOXIC HERBICIDES.
Source: 13TH ANNUAL MEETING OF THE SOCIETY FOR EPIDEMIOLOGIC RESEARCH,
MINNEAPOLIS, MINN., USA, JUNE 18-20, 1980. AM J EPIDEMIOL; 112 (3). 1980.
444. Keywords include: DIOXIN, MALIGNANCY, KIDNEY CANCER
Go to:
Introduction
to PCBs and Kidney Cancer
Summary
of Study Results
Studies
of PCBs and Kidney, Bladder and Urothelial Cancers
Links
to More Information
References
|