PMID:22029400
| Citation |
Jasti, VP, Spratt, TE and Basu, AK (2011) Tobacco-specific nitrosamine-derived O2-alkylthymidines are potent mutagenic lesions in SOS-induced Escherichia coli. Chem. Res. Toxicol. 24:1833-5 |
|---|---|
| Abstract |
To investigate the biological effects of the O(2)-alkylthymidines induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), we have replicated a plasmid containing O(2)-methylthymidine (O(2)-Me-dT) or O(2)-[4-(3-pyridyl-4-oxobut-1-yl]thymidine (O(2)-POB-dT) in Escherichia coli with specific DNA polymerase knockouts. High genotoxicity of the adducts was manifested in the low yield of transformants from the constructs, which was 2-5% in most strains but increased 2-4-fold with SOS. In the SOS-induced wild type E. coli, O(2)-Me-dT and O(2)-POB-dT induced 21% and 56% mutations, respectively. For O(2)-POB-dT, the major type of mutation was T → G followed by T → A, whereas for O(2)-Me-dT, T → G and T → A occurred in equal frequency. For both lesions, T → C also was detected in low frequency. The T → G mutation was reduced in strains with deficiency in any of the three SOS polymerases. By contrast, T → A was abolished in the pol V(-) strain, while its frequency in other strains remained unaltered. This suggests that pol V was responsible for the T → A mutations. The potent mutagenicity of these lesions may be related to NNK mutagenesis and carcinogenesis. |
| Links |
PubMed PMC3221470 Online version:10.1021/tx200435d |
| Keywords |
Carcinogens/toxicity; Chromatography, High Pressure Liquid; Colony Count, Microbial; DNA Adducts/chemistry; DNA Adducts/genetics; DNA Adducts/metabolism; DNA Damage/drug effects; DNA Replication/drug effects; DNA-Directed DNA Polymerase/genetics; DNA-Directed DNA Polymerase/metabolism; Escherichia coli/drug effects; Escherichia coli/genetics; Escherichia coli/metabolism; Gene Knockout Techniques; Isoenzymes/genetics; Isoenzymes/metabolism; Mutagenesis; Mutagens/adverse effects; Mutagens/toxicity; Nitrosamines/adverse effects; Nitrosamines/toxicity; Plasmids/genetics; Plasmids/metabolism; Pyridines/chemistry; Pyridines/metabolism; SOS Response (Genetics)/drug effects; Spectrometry, Mass, Electrospray Ionization; Thymidine/analogs & derivatives; Thymidine/genetics; Thymidine/metabolism; Tobacco/chemistry |
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