title: [Increase of general toxic effects and decrease of hepatocarcinogenic effects of diethylnitrosamine administered to mice in conjunction with isopropanol].
abstract: It is considered that diethylnitrosamine (DENA) is metabolized mostly in the liver with producing highly reactive compounds alkylating cellular macromolecules and causing toxic and carcinogenic effects. However, competitive inhibition of cytochrome P450 2E1, which metabolizes DENA, by its other substrate, isopropanol, does not weaken, but enhances the toxicity of DENA effect on mice and reduces the number of preneoplastic nodules and liver tumors induced by it. In short-term tests for mutagenicity (in the Ames test and the SOS-hromotest) DENA causes moderate damage of DNA that reduces liver microsomal enzymes, that metabolize nitrosamines. The obtained data indicate the predominant role of the initial compound as compared to its metabolites in toxic, and probably hepatocarcinogenic, effects on DNA in mice.
authors.forename: V I
authors.initials: VI
authors.lastname: Kaledin
authors.forename: N V
authors.initials: NV
authors.lastname: Baginskaia
authors.forename: E A
authors.initials: EA
authors.lastname: Vasiunina
authors.forename: S I
authors.initials: SI
authors.lastname: Il'nitskaia
authors.forename: L P
authors.initials: LP
authors.lastname: Ovchinnikova
mesh_terms: D019840:2-Propanol / Q000008:administration & dosage / Q000633:toxicity*; D000477:Alkylating Agents / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000633:toxicity*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism
chemical_list: D000477:Alkylating Agents; D002273:Carcinogens; D004052:Diethylnitrosamine; D019392:Cytochrome P-450 CYP2E1; D019840:2-Propanol