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Tumor-Promoting, Initiating, and Hepatotoxic Effects of 3,4,3',4'-Tetrabromobiphenyl (34-TBB) in Rats

Department of Pathology Michigan State University East Lansing, MI 48824

S.D. Sleight

The Rockefeller University, Laboratory Animal Research Center, New York, New York.

S.D. Aust

Department of Biochemistry, Michigan State University, East Lansing, Michigan.

M.S. Rezabek

The Rockefeller University, Laboratory Animal Research Center, New York, New York.

Female, 180–200 g Sprague-Dawley rats were used to determine if 3,4,3',4'-tetrabromobi-phenyl (34-TBB) is a promoter or initiator in a two-stage hepatocarcinogenesis assay. To test for promotion, rats were partially hepatectomized (PH) 24 hr before initiation (day 1) with 10 mg of diethylnitrosamine (DEN)/kg body weight given intraperitoneally (IP). Thirty days later, promotion was with 34-TBB (0.1,1 or 5 mg/kg) or phenobarbital (PB) (500 mg/kg) in diets for 180 days. To test for initiation, rats were PH and were initiated on day 1 with 34-TBB (1, 5, or 10 mg/kg) orally or DEN (10 mg/kg) IP. On day 31, promotion was with 500 mg of PB/kg of diet for 180 days. Noninitiated and non-PH rats were used to assess the histological and ultrastructural tissue changes associated with administration of 34-TBB in the diet for 180 days. Tumor promotion-initiation were assessed by counting and measuring hepatic enzyme-altered foci (EAF) with gamma-glutamyl transpeptidase (GGT) activity. Congener 34-TBB acts as a promoter in experimental hepatocarcinogenesis in rats, as evidenced by increased numbers of GGT-positive EAF. Also, 34-TBB may have initiation potential, as suggested by increased numbers of EAF in rats initiated with 34-TBB and promoted by PB. Dietary administration of 34-TBB for 180 days is not severely toxic in rats, as evidenced by mild histological and ultrastructural changes and minimal alterations in organ and body weights. Congener 34-TBB does not accumulate in liver and adipose tissue of rats.

International Journal of Toxicology, Vol. 7, No. 5, 687-697 (1988)
DOI: 10.3109/10915818809019543


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