Fate of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in pregnant and newborn C57BL mice.
Whole-body autoradiography of pregnant C57Bl mice injected intravenously with the tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), indicated that NNK and/or its metabolites can diffuse through the placenta and reach the fetal tissues. During the last days of gestation, nasal, pulmonary and hepatic tissues develop the enzymatic capacity to activate NNK to alkylating species which bind covalently to cellular macromolecules. Within 4 h of the injection, a considerable proportion of NNK metabolites present in the fetal tissues are excreted in the amniotic fluid via the fetal urinary tract. Incubation of tissue slices with NNK indicated that the nose, the lung and the liver of 13-day-old fetuses could reduce NNK to 4-(methylnitrosamino)-1-(3-pyridyl)butan -1-ol (NNA1), but could not activate NNK by alpha-carbon hydroxylation. However, these activating enzymes were competent in 18-day old fetuses, and the activities increased during the first six days of life. The results provide evidence that NNK could exert genotoxic effects transplacentally and in newborn mice.
D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D002273:Carcinogens / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009602:Nitrosamines / Q000378:metabolism* / Q000633:toxicity; D010947:Plants, Toxic; D011247:Pregnancy; D011270:Pregnancy, Animal; D014018:Tissue Distribution; D014026:Nicotiana
D002273:Carcinogens; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone