OXIDATIVE DEMETHYLATION OF N-METHYLHYDRAZINES BY RAT LIVER MICROSOMES

Certain N-methylhydrazines were found to be oxidatively demethylated to yield formaldehyde by rat liver microsomal preparations. Substrates for the N-demethylase were found to be monomethylhydrazine, 1,1-dimethylhydrazine, 1,2-dimethylhydrazine, Procarbazine, and the azo derivative of Procarbazine. Oxygen and a NADPH-regenerating system were required for maximum activity. Carbon monoxide inhibited the demethylation reaction but no inhibition was found by SKF 525-A. Phenobarbital or 3-methylcholanthrene pretreatment of the animals caused an enhancement of the demethylase activity. P-450 appears to play a role in the phenobarbital-inducible reaction since treatment of the microsomes with steapsin or deoxycholate which convert P-450 to P-420 inhibited only the induced activity. © 1969.