Biochemical studies of promoters of carcinogenesis in rat liver |
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Authors: | K T Kitchin J L Brown |
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Institution: | Experimental Dosimetry Branch (MD-74), U.S. Environmental Protection Agency, Research Triangle Park, North Carolina. |
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Abstract: | Adult female rats were orally dosed with 1/5 to 3/5 the published LD50 of either promoters or putative promoters of carcinogenesis hexachlorobenzene (HCB), alpha-hexachlorocyclohexane (alpha-HCH), kepone and toxaphene] or noncarcinogens coumaphos, EDTA, caprolactam, 8-hydroxyquinoline, titanium (IV) oxide, sodium diethyldithiocarbamate (DEDTC), and sucrose] at 21 and 4 h before sacrifice. The promoters selected in this study were all of the halogenated hydrocarbon class. At doses of 1/5 to 3/5 the LD50, all four promoters or putative promoters induced rat hepatic ODC activity. The seven noncarcinogens produced several biochemical effects at doses of 1/5 the LD50: increased serum alanine aminotransferase activity (SGPT) (caprolactam and DEDTC), decreased hepatic cytochrome P-450 content (DEDTC), and increased hepatic ODC activity (8-hydroxyquinoline and DEDTC). None of the seven noncarcinogens caused hepatic DNA damage or coordinate induction of hepatic ODC and cytochrome P-450. The results support the interpretation that several of these biochemical parameters are useful in distinguishing potential tumor promoters and noncarcinogens. |
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