Analysis of methyl DNA adducts and metabolites in BEAS-2B cells induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone

Analysis of methyl DNA adducts and metabolites in BEAS-2B cells induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
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4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁酮诱导的BEAS-2B细胞甲基DNA加合物和代谢物分析

DOI:
10.1080/15376516.2019.1611982
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发表时间:
2019-05
影响因子:
3.2
通讯作者:
Xie Fuwei
Xie Fuwei
中科院分区:
医学4区
文献类型:
--
作者:
Wang Huiting;Li Xiang;Zhao Ge;Xu Liangtao;Wang Sheng;Nie Mingxuan;Hua Chenfeng;Shang Pingping;Pan Lining;Zhao Junwei;Qiao Liangjun;Liu Kejian;Hu Kai;Su Jiakun;Cai Jibao;Xie Fuwei

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摘要 烟草特有的亚硝胺4 -(甲基亚硝胺基)-1 -(3 -吡啶基)-1 -丁酮(NNK)被归类为1类人类致癌物。它被细胞色素P450酶代谢激活为中间体,使DNA甲基化和吡啶氧丁基化,从而导致……
Abstract The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is classified as a Group 1 human carcinogen. It is metabolically activated by P450 enzymes to intermediate methylate and pyridyloxobutylate DNA, resulting in the formation of DNA adduct that is critical for the carcinogenicity of NNK. To directly and objectively examine the DNA adduct formation profiles without the complexity of factors in vivo, in the present study, five kinds of methyl DNA adducts were first identified in the incubation model of NNK established with human lung epithelial cells (BEAS-2B). The level of methyl DNA adducts and metabolites of NNK were quantitatively analyzed, respectively. With the increase of exposure time and dose, the level of methyl DNA adducts and metabolites increased. Furthermore, with the changes of the activity of P450 enzymes, which is the main enzyme regulating the α-hydroxylation of NNK, we found the levels of both methyl adducts and metabolites formed via α-hydroxylation in experimental groups showed the same trend compared with those in control group, while the metabolites formed via other pathways changed in the opposite trend. The result proves that the methyl adducts induced by NNK generate via α-hydroxylation pathway in BEAS-2B cells.
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