title: Effects of 8-methoxypsoralen on the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in mice.
abstract: 8-Methoxypsoralen (8-MOP) is a well established drug in the treatment of various skin diseases. Pretreatment of mice with 8-MOP before administration of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) significantly reduced the incidence of NNK-induced tumor. The present study was designed to evaluate the in vivo effects of 8-MOP on the bioactivation of NNK in mice. Decrease in the α-hydroxylation of NNK in mouse blood and tissues was observed as the most pronounced effect of 8-MOP. The catalytic property of cytochrome P450 2A5 (CYP2A5) enzyme in mice was determined by the coumarin 7-hydroxylation reaction, suggesting that 8-MOP produced remarkable inhibition on CYP2A5 in female C57BL/6 mice. These results implied that 8-MOP could prevent NNK-induced mutagenesis and tumorigenesis in mice through the inhibition of NNK α-hydroxylation, which may be achieved through the effect of 8-MOP on the bioactivities of CYP2A5.
authors.affiliation: Zhengzhou Tobacco Research Institute of CNTC, Zhengzhou 450001, China.
authors.forename: Mingfei
authors.initials: M
authors.lastname: Feng
authors.affiliation: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
authors.forename: Hongtu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Tobacco Production Technology Center, Bijie Tobacco Company of Guizhou Province, Bijie 551700, China.
authors.forename: Baojun
authors.initials: B
authors.lastname: Cao
authors.affiliation: Zhengzhou Tobacco Research Institute of CNTC, Zhengzhou 450001, China.
authors.forename: Shuaidong
authors.initials: S
authors.lastname: Liu
authors.affiliation: Zhengzhou Tobacco Research Institute of CNTC, Zhengzhou 450001, China. Electronic address: 20012188mj@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Mao
authors.affiliation: Zhengzhou Tobacco Research Institute of CNTC, Zhengzhou 450001, China. Electronic address: qdzhangcn@163.com.
authors.forename: Qidong
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D063646:Carcinogenesis / Q000139:chemically induced; D002273:Carcinogens; D002384:Catalysis / Q000187:drug effects; D003374:Coumarins / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D005260:Female; D006900:Hydroxylation / Q000187:drug effects; D007093:Imidazoles / Q000378:metabolism; D008730:Methoxsalen / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009602:Nitrosamines / Q000009:adverse effects / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D003374:Coumarins; D007093:Imidazoles; D009602:Nitrosamines; C517283:coumarin 7; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D001189:Aryl Hydrocarbon Hydroxylases; C585520:Cyp2a5 protein, mouse; D000072467:Cytochrome P450 Family 2; D008730:Methoxsalen
keywords: 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone; 8-Methoxypsoralen; Activity; CYP2A5; Metabolites; Mice