Enhancement of toxic and reduction of hepatocarcinogenic effects of diethylnitrosamine under its administration to mice in conjunction with isopropanol
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 his other substrate, isopropanol, not weakens 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 in adding of liver microsoma enzymes, which metabolize nitrosamines. The obtained data indicate on predominant role of the initial compound as compared to its metabolites in toxic and probably hepatocarcinogenic effects of DNA in mice.