Studies on the metabolism of dimethylnitrosamine in vitro by rat-liver preparations. III. Effect of cobaltous chloride treatment.

Abstract

1. The effects of CoCl2 administration to rats on xenobiotic metabolism, dimethylnitrosamine (DMN) metabolism to formaldehyde and methanol, and monoamine oxidase (MAO) enzyme activities in hepatic subcellular fractions have been studied. 2. CoCl2 treatment markedly decreased hepatic mixed-function oxidase enzyme activities and microsomal cytochrome P-450 content. In contrast, the N-oxidation of N, N-dimethylaniline and the activity of microsomal NADPH-cytochrome c reductase was unaffected. 3. The metabolism of DMN to formaldehyde by postmitochondrial supernatant fractions was decreased at substrate concn. of 0 . 5, 5 and 50 mM by CoCl2 treatment but the metabolism of 5 and 50 mM DMN to methanol was affected less. 4. CoCl2 had little effect on MAO activities in whole homogenates, but microsomal MAO activities were markedly inhibited. 5. The inhibition of microsomal MAO indicates that CoCl2 is not a specific inhibitor of cytochrome P-450-dependent biotransformations and consequently the inhibition of DMN metabolism is not evidence of a wholly cytochrome P-450-dependent process.