Different effects of chemicals on metabolism of N-nitrosamines in rat liver

IARC Sci Publ. 1987:(84):181-2.

Abstract

The effects of phenobarbital (PB), 3-methylcholanthrene (MC), pyrazole (PY) and ethanol (EtOH) pretreatment on N-nitrosodimethylamine (NDMA), N-nitrosobutylmethylamine (NBMA) and N-nitrosomethylbenzylamine (NMBzA) metabolism were examined in rats. In isolated hepatocytes, PB increased the metabolic decomposition of NBMA and NMBzA, and MC increased that of NBMA; PY and EtOH increased only that of NDMA. In studies of hepatic microsomal dealkylation, PB increased NBMA debutylation and NMBzA debenzylation, and MC increased NBMA debutylation; PY and EtOH increased NDMA demethylation selectively. Several cytochrome P450 (P450) species were active in dealkylating nitrosamines, indicating that the organ-specific carcinogenicity of nitrosamines might be changed by various P450 inducers.

MeSH terms

  • Animals
  • Dimethylnitrosamine / analogs & derivatives
  • Dimethylnitrosamine / metabolism
  • Ethanol / pharmacology
  • Liver / drug effects*
  • Liver / metabolism
  • Methylcholanthrene / pharmacology
  • Nitrosamines / metabolism*
  • Phenobarbital / pharmacology
  • Pyrazoles / pharmacology
  • Rats

Substances

  • Nitrosamines
  • Pyrazoles
  • Ethanol
  • pyrazole
  • Methylcholanthrene
  • nitrosobenzylmethylamine
  • Dimethylnitrosamine
  • Phenobarbital