PCBs and Liver Cancer - Upcoming Research

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PCBs and Liver Cancer in Humans

Upcoming Research ---

ROBERTSON LW. MECHANISMS OF CARCINOGENESIS--HALOGENATED BIPHENYLS. Crisp Data Base National Institutes Of Health. Author Address: 204 FUNKHOUSER BLDG, LEXINGTON, KY 40506-0054

PCBs may cause liver cancer by:

inducing mutations, cytogenetic damage and cell transformation
forming quinoid and expoxide metabolites that (at least in part) are responsible for genotoxic effects
inducing DNA adducts

Polyhalogenated biphenyls, particularly polychlorinated biphenyls (PCBs), are industrial chemicals which are stable and persist in our environment. Their lipophilicity and resistance to chemical or biological degradation result in their accumulation in fatty tissues of humans and other animals and eventual secretion into milk fat. These characteristics raise concern about the health risks associated with long-term exposure to these compounds. Numerous studies have found that PCBs and the closely-related polybrominated biphenyls (PBBs) induce hepatocellular carcinomas in mice and rats, but the mechanism by which they do so has not been determined. We and others have shown that PCBs/PBBs act as promoters of liver carcinogenesis; but their initiating or DNA-damaging activity has not been conclusively demonstrated. We therefore propose to test the hypotheses that biphenyl and halogenated biphenyls 1) induce mutations, cytogenetic damage and cell transformation in in vitro systems, 2) form quinoid metabolites that (at least in part) are responsible for genotoxic effects seen, 3) induce DNA adducts in rats. The potential of biphenyl and halogenated biphenyls to induce mutations in mammalian cells will be examined, while their ability to interact with cellular DNA will be monitored by sensitive 32P-postlabeling methods. Of particular interest is the identification of the reactive species responsible for the genotoxicity. Using these test systems, we shall define structure-activity relationships, identify critical metabolic parameters (which enzymes, cofactors are involved), identify mammalian targets and determine the structures of active metabolites. Our preliminary data indicate that several lower halogenated biphenyls are mutagenic in Salmonella and in V79 cells in the presence of an exogenous activation system. The spectra of genotoxicity seen with these compounds indicate that two mechanisms of activation (via expoxides and quinones) are operative. Our most recent data showing that mono- and dichlorobiphenyls are enzymatically activated to species that form adducts with guanine and/or adenine strongly support the involvement of quinones in the genotoxicity of these compounds. Clarification of the mechanism by which individual PCBs cause liver tumors will form a basis for the human health risk assessment for exposure to these chemicals.

Studies Without Abstracts

Urabe H, Koda H, Asahi M. Present state of Yusho patients. Ann NY Acad Sci 1979;320:273-6.

Kuratsune M. Epidemiologic studies on Yusho. In: Higuchi K, ed. PCB poisoning and pollution. Tokyo: Kodansha Ltd., 1976:9-23.

TSUJI H, AKAGI K, MURAI K, KAJIWARA E, FUJISHIMA M. LIVER DAMAGE AND HEPATOCELLULAR CARCINOMA IN PATIENTS WITH YUSHO. FUKUOKA ACTA MED; 78 (5). 1987. 343-348. Keywords: HEPATITIS B VIRUS SURFACE ANTIGEN POLYCHLORINATED BIPHENYLS ENVIRONMENTAL TOXIN SERUM GLUTAMIC OXALACETIC TRANSAMINASE GLUTAMIC PYRUVIC TRANSAMINASE ALKALINE
PHOSPHATASE GAMMA GLUTAMYL TRANSPEPTIDASE ALCOHOL CONSUMPTION CIRRHOSIS OBESITY

OKUMURA M, SAKAGUCHI S. HEPATIC CELL CARCINOMA AND THE PATIENTS WITH YUSHO

FUKUOKA ACTA MED; 76 (5). 1985. 229-232. Keywords: HEPATITIS B VIRUS MARKER HEPATITIS B VIRUS SURFACE ANTIGEN ALPHA FETOPROTEIN POLYCHLORINATED BIPHENYL ULTRASOUND EXAMINATION CHRONIC LIVER DISEASE HEPATIC CIRRHOSIS

KURATSUNE M, NAKAMURA Y, IKEDA M, HIROHATA T. ANALYSIS OF DEATHS SEEN AMONG PATIENTS WITH YUSHO A PRELIMINARY REPORT. MEETING ON CHLORINATED DIOXINS AND RELATED COMPOUNDS HELD AT THE SIXTH INTERNATIONAL SYMPOSIUM, FUKUOKA, JAPAN, SEPTEMBER 16-19, 1986. CHEMOSPHERE; 16 (8-9). 1987. 2085-2088. Keywords: POLYCHLORINATED BIPHENYLS POLYCHLORINATED DIBENZOFURANS POLYCHLORINATED QUATERPHENYLS LIVER CANCER CONTAMINATED RICE OIL

Kikuchi M, Shigematsu N, Umeda G. Autopsy report of two yusho patients who died nine years after onset. Fukuoka Igaku Zasshi 1979 Apr;70(4):215-22

BOYER TD. ENVIRONMENTAL AGENTS IN THE CAUSE OF HEPATIC MALIGNANCIES. BECKER, C. E. AND M. J. COYE (ED.). CANCER PREVENTION: STRATEGIES IN THE WORKPLACE; SECOND ANNUAL OCCUPATIONAL CANCER CONFERENCE, SAN FRANCISCO, CALIFORNIA, USA, 1984. XI+155P. HEMISPHERE PUBLISHING CORPORATION: WASHINGTON, DISTRICT OF COLUMBIA, USA; CAMBRIDGE, ENGLAND. ISBN 0-89116-441-3.; 0 (0). 1986. 73-82. REVIEW HUMAN ANIMAL MODELS NITROSAMINES ACETYLAMINOFLUORENE POLYCHLORINATED BIPHENYLS VINYL CHLORIDE AFLATOXINS THOROTRAST ARSENIC STERIGMATOCYSTINS CYCLOCHLOROTINE CYCASIN PYRROLIZIDINE ALKALOIDS HEPATITIS B VIRUS HEPATOCELLULAR CARCINOMA SMOKING FOODSTUFF CONTAMINATION VACCINE

Links to More Information

The Liver Cancer Network

http://www.livercancer.com/index.html

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