Influence of cell proliferation on initiating activity of pure polychlorinated biphenyls and complex mixtures in resistant hepatocyte in vivo assays for carcinogenicity1, 2, 3

M. Anthony Hayes, Ross G. Cameron, Dianna Armstrong, Stephen H. Safe

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1037-1041
Number of pages5
JournalJournal of the National Cancer Institute
Volume74
Issue number5
DOIs
StatePublished - May 1 1985

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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