In vitro genotoxicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone activated by hamster maternal and fetal tissues.
The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was found to be a potent genotoxic agent, in the V79 cell line, when activated by liver and lung homogenates from polychlorinated biphenyl (Aroclor)-treated adult Syrian golden hamsters. The damage was observed in the metaphase as well as in the anaphase--telophase divisions. Liver and lung homogenates from non-induced adult hamster were less effective in activating NNK. Micronuclei were also induced by NNK activated by fetal liver and lung homogenates from fetuses on the 15th day of gestation. The observed aberrations: micronuclei, chromatid aberrations particularly chromatid-type exchanges, anaphase bridges with or without acentric fragments, were concentration (8-40 mM NNK)-dependent. A significant number of aberrations were observed. These results suggest that NNK induces chromosome damage when activated by adult and fetal tissues. This damage could play, at least in part, a role in the NNK-induced carcinogenesis observed in vivo and underlines the importance of this compound in the transplacental carcinogenesis induced by tobacco smoke.
Alaoui-Jamali
M A
MA
School of Pharmacy, Université Laval, Quebec City, Canada.
Castonguay
A
A
Schuller
H M
HM
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D002869:Chromosome Aberrations; D006224:Cricetinae; D005260:Female; D005333:Fetus / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000378:metabolism; D008647:Mesocricetus; D009153:Mutagens / Q000378:metabolism*; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity*; D010947:Plants, Toxic; D011247:Pregnancy; D014026:Nicotiana
D002273:Carcinogens; D009153:Mutagens; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone