Alaoui-Jamali M A, Massey T E, Douglas A, Rossignol G, Castonguay A
Laboratory of Cancer Etiology and Chemoprevention, School of Pharmacy, Laval University, Quebec, Canada.
Cancer Lett. 1990 Jun 30;52(1):49-55. doi: 10.1016/0304-3835(90)90076-a.
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.
尼古丁衍生的N-亚硝胺，4-（甲基亚硝基氨基）-1-（3-吡啶基）-1-丁酮（NNK），是叙利亚金黄地鼠中一种强效的呼吸道致癌物。比较了三种富集的肺细胞群体对NNK的体外代谢情况。克拉拉细胞通过α-碳羟基化激活NNK的能力比肺泡巨噬细胞和成纤维细胞高十多倍。在前述细胞类型中，吡啶N-氧化使NNK失活的水平比α-碳羟基化低十倍。在肺泡巨噬细胞中，羰基还原是主要的代谢途径。我们的结果表明，NNK在仓鼠肺中诱导的DNA损伤更有可能发生在克拉拉细胞中，而不是巨噬细胞或成纤维细胞中。
