Decreased clastogenicity of dinitropyrenes in Chinese hamster lung (CHL) subclone cells with low NADPH-cytochrome P-450 reductase activity

Mutat Res. 1991 Sep;264(1):37-41. doi: 10.1016/0165-7992(91)90043-4.

Abstract

Clastogenic potentials of 1,3-, 1,6- and 1,8-dinitropyrenes (DNPs) were compared between Chinese hamster lung (CHL) cells and its subclone MM1 cells, which were recently isolated as menadione-resistant cells after treatment with MNNG. NADPH-cytochrome P-450 reductase activity of the MM1 cells decreased to 50% of that in the parental CHL cells. All 3 DNPs induced chromosomal aberrations without exogenous metabolic activation systems in the CHL cells. 1,6- and 1,8-DNP showed equivalent clastogenic potency: the maximum frequency of cells with chromosomal aberrations was about 50% for both chemicals. The clastogenic potential of 1,3-DNP was lower than that of 1,6- and 1,8-DNP: the maximum frequency of aberrant cells was 10%. In the MM1 cells, in contrast, the frequencies of aberrant cells decreased to about 30% of those observed for the parental CHL cells after treatment with 1,6- and 1,8-DNP, and to the same level as that of the concurrent control after treatment with 1,3-DNP. These results suggest a possibility that the reduced clastogenic effect of 3 DNPs in MM1 cells may correlate with the reduced activity of NADPH-cytochrome P-450 reductase which is thought to contribute to the metabolic conversion of these DNPs to their clastogenic forms in the CHL cells.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biotransformation
  • Cell Line
  • Chromosome Aberrations
  • Cricetinae
  • Cricetulus
  • Drug Resistance
  • Lung / cytology
  • Methylnitronitrosoguanidine / toxicity
  • Mutagenicity Tests
  • Mutagens / metabolism
  • Mutagens / toxicity*
  • NADPH-Ferrihemoprotein Reductase / genetics
  • NADPH-Ferrihemoprotein Reductase / metabolism*
  • Pyrenes / metabolism
  • Pyrenes / toxicity*
  • Vitamin K / pharmacology

Substances

  • Mutagens
  • Pyrenes
  • Vitamin K
  • Methylnitronitrosoguanidine
  • 1,8-dinitropyrene
  • 1,6-dinitropyrene
  • 1,3-dinitropyrene
  • NADPH-Ferrihemoprotein Reductase