Influence of cell proliferation on initiating activity of pure polychlorinated biphenyls and complex mixtures in resistant hepatocyte in vivo assays for carcinogenicity

• Published in: JNCI : Journal of the National Cancer Institute Vol. 74; no. 5; p. 1037
• Main Authors: Hayes, M A, Safe, S H, Armstrong, D, Cameron, R G
• Format: Journal Article
• Language: English
• Published: United States 01.05.1985
• Subjects: Animals; Animals, Newborn; Carcinogens; Cell Division - drug effects; Cell Transformation, Neoplastic - chemically induced; Cell Transformation, Neoplastic - enzymology; Cocarcinogenesis; Enzyme Induction - drug effects; Female; gamma-Glutamyltransferase - biosynthesis; Hepatectomy; Liver - drug effects; Liver - pathology; Liver Neoplasms - chemically induced; Male; Polychlorinated Biphenyls - toxicity; Rats; Rats, Inbred F344
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/74.5.1037

The abilities of various pure polychlorinated biphenyls (PCB) and complex mixtures to generate resistant gamma-glutamyltransferase (GGT)-positive hepatocellular nodules was evaluated in F344 rats in which hepatocytes were proliferating. The PCB examined were 2,2',4,4',5,5'-hexachlorobiphenyl (CAS: 35065-27-1), 2,2',4,4'-tetrachlorobiphenyl, 2,2',5,5'-tetrachlorobiphenyl, Aroclor 1254 (CAS: 11097-69-1), and a prepared mixture of pure PCB isomers and congeners similar to those found in human breast milk. The PCB were administered either to male and female suckling rats (weekly for 3 wk) during liver growth or to adult male rats (150-160 g body wt) previously subjected to two-thirds partial hepatectomy (PH). Rats were subsequently given a selection regimen consisting of 3 daily doses (20 mg/kg) of 2-acetylamino-fluorene (2-FAA; CAS: 53-96-3) followed by either PH or necrotizing carbon tetrachloride (CAS: 56-23-5) in adult rats that previously underwent PH. None of the PCB exposures generated GGT-positive nodules after selection, whereas known initiators such as diethylnitrosamine (CAS: 55-18-5), 3-methylcholanthrene (CAS: 56-49-5), benzo[a]pyrene (CAS: 50-32-8), and 2-FAA were active initiators of nodules in suckling or hepatectomized rats. These findings indicate that short-term exposures to these PCB during liver cell proliferation do not show initiating action in an in vivo assay that detects both hepatic and nonhepatic initiating carcinogens.