Biochemical studies of promoters of carcinogenesis in rat liver.
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.
Kitchin
K T
KT
Experimental Dosimetry Branch (MD-74), U.S. Environmental Protection Agency, Research Triangle Park, North Carolina.
Brown
J L
JL
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002273:Carcinogens; D002470:Cell Survival; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D006846:Hydrocarbons, Halogenated; D003577:Cytochrome P-450 Enzyme System; D000410:Alanine Transaminase; D009955:Ornithine Decarboxylase