Influence of cell proliferation on initiating activity of pure polychlorinated biphenyls and complex mixtures in resistant hepatocyte in vivo assays for carcinogenicity^{1, 2, 3}

The abilities of various pure polychlorinated biphenyls (PCB) and complex mixtures to generate resistant γ-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 (150160 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-ftuorene (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.