title: In vitro metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by lung cells isolated from Syrian golden hamster.
abstract: The nicotine derived N-nitrosamine, 4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone (NNK), is a potent respiratory carcinogen in the Syrian golden hamster. The in vitro metabolism of NNK by three enriched lung cell populations were compared. Clara cells had more than ten times higher capacity to activate NNK by alpha-carbon hydroxylation than alveolar macrophages and fibroblasts. In the former cell types, levels of deactivation of NNK by pyridine N-oxidation were ten times lower than those of alpha-carbon hydroxylation. In alveolar macrophages, carbonyl reduction was the major metabolic pathway. Our results suggest that DNA damages induced by NNK in hamster lung is more likely to occur in Clara cells than in macrophages or fibroblasts.
authors.affiliation: Laboratory of Cancer Etiology and Chemoprevention, School of Pharmacy, Laval University, Quebec, Canada.
authors.forename: M A
authors.initials: MA
authors.lastname: Alaoui-Jamali
authors.forename: T E
authors.initials: TE
authors.lastname: Massey
authors.forename: A
authors.initials: A
authors.lastname: Douglas
authors.forename: G
authors.initials: G
authors.lastname: Rossignol
authors.forename: A
authors.initials: A
authors.lastname: Castonguay
mesh_terms: D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000493:pharmacokinetics*; D002452:Cell Count; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D006224:Cricetinae; D005347:Fibroblasts / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009602:Nitrosamines / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction
chemical_list: D002273:Carcinogens; D009602:Nitrosamines; C047760:4-(methylnitrosamino)-4-(3-pyridyl)butanal