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 50mM by CoCl₂ treatment but the metabolism of 5 and 50mM 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.