Metabolism and mutagenicity of N-nitrosohexamethyleneimine and its hydroxylated derivatives

Teratog Carcinog Mutagen. 1983;3(1):9-17. doi: 10.1002/1520-6866(1990)3:1<9::aid-tcm1770030103>3.0.co;2-f.

Abstract

There is a direct relationship between the metabolism and mutagenicity of N-nitrosohexamethyleneimine (NO-HEX) in the presence of uninduced and AC- and PB-induced S8 and S9 fractions from rats and hamsters. Although alpha-hydroxylation is the most important process in the formation of mutagens, NO-HEX may be hydroxylated on the beta- and gamma-carbon atoms as well. beta- and gamma-hydroxyNO-HEX do not appear to play a significant role in the total mutagenicity of NO-HEX. Using rat liver subcellular fractions, beta- and gamma-hydroxyNO-HEX are only marginally mutagenic compared with NO-HEX. With hamster S9 fractions, beta-hydroxyNO-HEX is equally as mutagenic as NO-HEX itself, but gamma-hydroxyNO-HEX is a much less potent mutagen. However, beta-hydroxyNO-HEX is produced in small amounts and therefore does not contribute greatly to the total mutagenicity of NO-HEX.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biotransformation
  • Cricetinae
  • Hydroxylation
  • Kinetics
  • Male
  • Mesocricetus
  • Microsomes, Liver / metabolism*
  • Mutagenicity Tests
  • Mutagens / metabolism*
  • Mutagens / pharmacology
  • Mutation*
  • Nitrosamines / metabolism*
  • Nitrosamines / pharmacology
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Strains
  • Salmonella typhimurium / drug effects
  • Structure-Activity Relationship

Substances

  • Mutagens
  • Nitrosamines
  • N-nitrosoperhydroazepine