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

Autor:	Liu Kejian, Wang Huiting, Zhao Junwei, Jiakun Su, Jibao Cai, Ge Zhao, Pingping Shang, Hu Kai, Qiao Liangjun, Sheng Wang, Liangtao Xu, Xiang Li, Hua Chenfeng, Mingxuan Nie, Fuwei Xie, Pan Lining
Rok vydání:	2019
Předmět:	Nitrosamines Health Toxicology and Mutagenesis Metabolite Cell Culture Techniques 010501 environmental sciences Hydroxylation Toxicology 01 natural sciences Cell Line Adduct DNA Adducts 03 medical and health sciences chemistry.chemical_compound Cytochrome P-450 Enzyme System In vivo DNA adduct Humans Lung Carcinogen 0105 earth and related environmental sciences chemistry.chemical_classification 0303 health sciences Dose-Response Relationship Drug 030302 biochemistry & molecular biology Epithelial Cells DNA Methylation Enzyme chemistry Biochemistry Nitrosamine Carcinogens DNA
Zdroj:	Toxicology Mechanisms and Methods. 29:499-510
ISSN:	1537-6524 1537-6516
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::198a51ee2e9ddc2d7ee5df181ae46741 https://doi.org/10.1080/15376516.2019.1611982 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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