The Stimulation of Lipid Peroxidation Produced by Dimethylnitrosamine in Rat Liver Microsomes in vitro: The Effects of Promethazine and Inhibitors of Drug Metabolism, and a Comparison with Previous Studies using Carbon Tetrachloride

Abstract

1. Addition of dimethylnitrosamine to rat liver microsomal suspensions increases the rate of NADPH-linked lipid peroxidation.

2. The stimulatory effects of dimethylnitrosamine on microsomal lipid peroxidation are decreased by inhibitors of microsomal oxidative drug metabolism and by promethazine, but are not altered by the substitution of the NADPH by an equimolar concn. of NADH.

3. Dimethylnitrosamine interacts with cytochrome P-450 as shown by the use of difference spectra, and the stimulation of lipid peroxidation probably depends upon metabolism of the dimethylnitrosamine at this site.

4. Results are compared and contrasted with previous data on the stimulation of lipid peroxidation by CCl₄.