Transplacental genotoxicity of a tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, in Syrian golden hamster.
NNK is abundant in cigarette smoke and is a potent respiratory carcinogen in adult Syrian golden hamsters. Micronucleus (MN) induction in fetal liver and maternal bone marrow polychromatic erythrocytes (PCEs) were assayed after i.p. injection of NNK to 14-day pregnant hamsters. The frequency of MN induction observed in fetal PCEs reached a maximum 18 h after treatment. The relationship dose NNK (0-200 mg/kg) to MN frequency was significant (P less than 0.005). In contrast no significant MN induction was observed in adult bone-marrow PCEs (P greater than 0.1). Extraction of fetal liver and amniotic fluid and HPLC separation of NNK metabolites revealed that NNK and its metabolite NNA1 could cross the placental barrier and be activated to protein-binding intermediates. These results suggest that NNK could be a transplancental carcinogen in Syrian golden hamsters.
Alaoui-Jamali
M A
MA
Laboratory of Cancer Etiology and Chemoprevention, School of Pharmacy, Laval University, Quebec City, Canada.
Rossignol
G
G
Schuller
H M
HM
Castonguay
A
A
D000818:Animals; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000648:ultrastructure; D005260:Female; D008099:Liver / Q000196:embryology; D008431:Maternal-Fetal Exchange; D008647:Mesocricetus; D015162:Micronucleus Tests; D009153:Mutagens; D009602:Nitrosamines / Q000633:toxicity*; D010947:Plants, Toxic; D011247:Pregnancy; D014026:Nicotiana
D009153:Mutagens; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone