Short-term oral administration of polybrominated biphenyls enhances the development of hepatic enzyme-altered foci in initiated rats.
FireMaster BP-6 (FM), a commercial mixture of polybrominated biphenyls (PBB), has been shown to act as a tumor promoter in hepatocarcinogenesis assays in rats. Most hepatic tumor promoters must be administered for many weeks or months. Because FM is highly persistent in animal tissues, it was hypothesized that very short-term administration of FM would result in tumor promotion. Female Sprague-Dawley rats weighing 185-215 g were initiated by a two-thirds partial hepatectomy followed by 10 mg diethylnitrosamine/kg body weight (BW) 24 h later. Thirty days later, rats were gavaged with FM in corn oil, at total doses of 0, 13, or 130 mg FM/kg BW. Half the dose was given on d 30, and the remaining half was given 24 h later. At 120 d after gavage the rats were killed and necropsied. Five liver sections from each animal were histochemically stained for gamma-glutamyl transpeptidase-positive enzyme-altered foci (EAF). EAF were significantly increased over control values in initiated rats given 130 mg FM/kg. In animals given 13 mg FM/kg, EAF were increased to a lesser extent but not significantly above controls. Enhancement of these EAF in initiated rats reflects tumor-promoting activity. In this study, 24-h administration of FM in initiated rats was sufficient to enhance hepatic EAF measured 120 d later in an rats was sufficient to enhance hepatic EAF measured 120 d later in an initiation-promotion protocol, and a dose of 13 mg FM/kg was apparently close to a possible no-effect threshold level for enhancement of EAF.
D000284:Administration, Oral; D000633:Aminopyrine N-Demethylase / Q000096:biosynthesis; D000818:Animals; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008862:Microsomes, Liver / Q000201:enzymology; D010088:Oxidoreductases / Q000096:biosynthesis; D011075:Polybrominated Biphenyls / Q000008:administration & dosage* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D011075:Polybrominated Biphenyls; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D000633:Aminopyrine N-Demethylase