Decreased clastogenicity of dinitropyrenes in Chinese hamster lung (CHL) subclone cells with low NADPH-cytochrome P-450 reductase activity.
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.
Sawada
M
M
Division of Genetics and Mutagenesis, National Institute of Hygienic Sciences, Tokyo, Japan.
Sofuni
T
T
Ishidate
M
M
D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance; D008168:Lung / Q000166:cytology; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics / Q000378:metabolism*; D011721:Pyrenes / Q000378:metabolism / Q000633:toxicity*; D014812:Vitamin K / Q000494:pharmacology
D009153:Mutagens; D011721:Pyrenes; D014812:Vitamin K; D008769:Methylnitronitrosoguanidine; C033310:1,8-dinitropyrene; C033309:1,6-dinitropyrene; C037413:1,3-dinitropyrene; D009251:NADPH-Ferrihemoprotein Reductase