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Analysis of methyl DNA adducts and metabolites in BEAS-2B cells induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
- Source :
- Toxicology Mechanisms and Methods. 29:499-510
- Publication Year :
- 2019
- Publisher :
- Informa UK Limited, 2019.
-
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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15376524 and 15376516
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Toxicology Mechanisms and Methods
- Accession number :
- edsair.doi.dedup.....198a51ee2e9ddc2d7ee5df181ae46741