Biochemical Studies of Promoters of Carcinogenesis in Rat Liver

摘要

Adult female rats were orally dosed with 1/5 the LD50 of either an initiator of carcinogens (1,2-dibromo-3-chloropropane (DBCP)), promoters or putative promoters of carcinogenesis (hexachlorobenzene, alpha-hexachlorocyclohexane, kepone and toxaphene) or noncarcinogens (coumaphos, EDTA, caprolactam, 8-hydroxyquinoline, titanium(IV)oxide, sodium diethyldithiocarbamate (DEDTC), and sucrose) at 21 and 4 hours before sacrifice. The initiator and promoters selected in the study were all of the halogenated hydrocarbon class. DBCP caused a large degree of hepatic DNA damage and an increase in hepatic ODC activity. At doses ranging between 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: serum alaine aminotransferase (SGPT) increases (caprolactam and DEDTC), decreased hepatic cytochrome P-450 (sucrose and DEDTC) and increased hepatic ODC (8-hydroxyquinoline and DEDTC). None of the seven noncarcinogens caused hepatic DNA damage or coordinate induction of hepatic ODC and cytochrome P-450.