The inhibition of cytochrome P450 2A13-catalyzed NNK metabolism by NAT, NAB and nicotine
文献类型：期刊论文
| 作者 | Liu, Xingyu2; Zhang, Jie2; Zhang, Chen2; Yang, Bicheng3; Wang, Limeng1,4; Zhou, Jun2 |
| 刊名 | TOXICOLOGY RESEARCH
 |
| 出版日期 | 2016 |
| 卷号 | 5期号:4页码:1115-1121 |
| ISSN号 | 2045-452X |
| DOI | 10.1039/c6tx00016a |
| 文献子类 | Article |
| 英文摘要 | 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is considered to be the most carcinogenic of the four tobacco-specific nitrosamines (TSNAs) and it needs to be metabolically activated to exert its carcinogenic effect on humans. For the simultaneous intake of NNK and other compounds with similar molecular structures in the context of tobacco smoke, whether (R,S)-N-nitrosoanatabine (NAT), (R,S)-N-nitrosoanabasine (NAB) and nicotine contribute to the inhibitory potency of the cytochrome P450 (CYP) enzyme-catalyzed NNK metabolism or not needs to be investigated. In the in vitro study, 4-oxo-4-(3-pyridyl) butanal (OPB), 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) and 4-oxo-4-(3-pyridyl) butanoic acid (OPBA) were established as the products of the CYP2A13-catalyzed NNK metabolism and the kinetic parameters were calculated from the Michaelis-Menten equation. Addition of NAT, NAB or nicotine resulted in a competitive inhibition for the NNK metabolism catalyzed by CYP2A13. The inhibition constant K-i values were calculated to be 0.21 mu M (NAT), 0.23 mu M (NAB) and 8.51 mu M (nicotine) for OPB formation; 0.71 mu M (NAT), 0.87 mu M (NAB) and 25.01 mu M (nicotine) for HPB formation and 0.36 mu M (NAT), 0.50 mu M (NAB) and 6.57 mu M (nicotine) for OPBA formation, respectively. In addition, the study of the transformation of the three metabolites revealed OPB was not only an end product but also an intermediate product of the CYP2A13-catalyzed NNK metabolism. These results suggest that structurally similar tobacco constituents with weak or no carcinogenicity influence the metabolic activation of NNK, which interferes with its carcinogenicity to some extent. |
| WOS关键词 | TOBACCO-SPECIFIC NITROSAMINES ; CARCINOGEN 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE NNK ; HUMAN LIVER-MICROSOMES ; HUMAN LUNG ; CIGARETTE-SMOKE ; BETA-NICOTYRINE ; N-NITROSAMINES ; A/J MICE ; ENZYMES ; ACTIVATION |
| WOS研究方向 | Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000378716100013 |
| 出版者 | ROYAL SOC CHEMISTRY |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/170432]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 通讯作者 | Liu, Xingyu |
| 作者单位 | 1.Univ Chinese Acad Sci, Dalian Inst Chem Phys, 457 Zhongshan Rd, Dalian 116023, Liaoning, Peoples R China 2.Shanghai Tobacco Grp Corp, 99 Wansheng South St, Beijing 101121, Peoples R China 3.Jiangxi Prov Maternal & Child Hlth Hosp, 318 Bayi Rd, Nanchang 330006, Jiangxi, Peoples R China 4.Zhengzhou Tobacco Res Inst, 2 Fengyang Rd, Zhengzhou 450001, Henan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Xingyu,Zhang, Jie,Zhang, Chen,et al. The inhibition of cytochrome P450 2A13-catalyzed NNK metabolism by NAT, NAB and nicotine[J]. TOXICOLOGY RESEARCH,2016,5(4):1115-1121. |
| APA | Liu, Xingyu,Zhang, Jie,Zhang, Chen,Yang, Bicheng,Wang, Limeng,&Zhou, Jun.(2016).The inhibition of cytochrome P450 2A13-catalyzed NNK metabolism by NAT, NAB and nicotine.TOXICOLOGY RESEARCH,5(4),1115-1121. |
| MLA | Liu, Xingyu,et al."The inhibition of cytochrome P450 2A13-catalyzed NNK metabolism by NAT, NAB and nicotine".TOXICOLOGY RESEARCH 5.4(2016):1115-1121. |
入库方式： OAI收割
来源：大连化学物理研究所
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