TY - JOUR
T1 - Influence of cell proliferation on initiating activity of pure polychlorinated biphenyls and complex mixtures in resistant hepatocyte in vivo assays for carcinogenicity1, 2, 3
AU - Hayes, M. Anthony
AU - Cameron, Ross G.
AU - Armstrong, Dianna
AU - Safe, Stephen H.
N1 - Funding Information:
I Received September 25, 1984; accepted January 14, 1985. 2 Supported by grant G0901 from the Natural Sciences and Engineering Research Council of Canada, by Public Health Service grant ES-02798 from the National Institute of Environmental Health Sciences, and by grants from Health and Welfare Canada and from the Center for Comparative Medicine (Texas A & M University). 3 Animals were maintained under the guidelines of the Canadian Council on Animal Care. 4 Department of Pathology, Medical Sciences Building, University of Toronto, Toronto, Ontario, Canada M5S lA8. S Department of Pathology, University of Guelph, Ontario Veterinary College, Guelph, Ontario, Canada NIG 2WJ. 6 Department of Veterinary Physiology and Pharmacology, Texas A & M University, College Station, TX 77843. 7 Scholar of the Canadian Liver Foundation. 8 Address reprint requests to Or. Cameron. 9 We thank Or. E. Farher for advice and Mrs. F. Keen for preparing the manuscript.
Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1985/5/1
Y1 - 1985/5/1
N2 - 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.
AB - 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.
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U2 - 10.1093/jnci/74.5.1037
DO - 10.1093/jnci/74.5.1037
M3 - Article
C2 - 2860266
AN - SCOPUS:0021857936
VL - 74
SP - 1037
EP - 1041
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
SN - 0027-8874
IS - 5
ER -