Stress, hormonal changes, alcohol, food constituents and drugs: Factors that advance the incidence of tobacco smoke-related cancer?

被引:32
作者
Maser, E
机构
[1] Dept. of Pharmacology and Toxicology, School of Medicine, Philipps-University of Marburg, D-35033 Marburg/Lahn
关键词
D O I
10.1016/S0165-6147(97)01090-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The genotoxicity of the most potent carcinogen in cigarette smoke [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)] is dependent on the relationship between its activation by cytochrome P450 enzymes and its detoxification by carbonyl reduction to NNK alcohol (NNAL) followed by glucuronidation. Recently, '11 beta-hydroxysteroid dehydrogenase' (11 beta-HSD 1) was identified to be responsible for NNK carbonyl reduction. It is now speculated that differences in tissue expression of 11 beta-HSD 1, as well as genetic polymorphisms, may have profound influences on the organospecificity and potency of NNK-induced cancerogenesis. Moreover, endogenous and exogenous substrates or inhibitors of 11 beta-HSD 1 may shift the NNK/NNAL equilibrium and favour MNK toxification in a variety of physiological and therapeutic situations. These issues are discussed here by Edmund Maser, who also describes how recent observations could provide the experimental base for epidemiological or clinical studies, which focus on polymorphisms in 11 beta-HSD 1 enzyme expression, as well as on implications of exposure to 11 beta-HSD 1 modulators and concurrent smoking.
引用
收藏
页码:270 / 275
页数:6
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