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A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s
Published on: September 25, 2017
The effects of 1-nitropyrene on oxidative DNA damage and expression of DNA repair enzymes
Yong-Dae Kim1, Young-Jun Ko, Toshihiro Kawamoto
1Department of Preventive Medicine & Medical Research Center, College of Medicine, Chungbuk National University, South Korea.
Abstract:
Nitropyrenes (NPs) present in diesel and gasoline emissions are mutagenic and carcinogenic in experimental animals. Nitro-reduction of 1-NP causes oxidative stress. It is unclear whether 8-hydroxydeoxyguanosine (8-OH-dG) is produced from 1-NP and whether it contributes to the carcinogenic activity of 1-NP. In this study, we measured the level of reactive oxygen species (ROS) in cultured human lung epithelial cells after exposure to 1-NP and the intracellular level of 8-OH-dG and expression level of the 8-OH-dG repair enzymes. As results, 1-NP induced the generation of 8-OH-dG via ROS, but 8-OH-dG repair enzymes prevented an increase of 8-OH-dG formation in cellular DNA of the A549 cell line below 250 microM of 1-NP. These data suggest that 1-NP can induce oxidative DNA damage by generation of ROS, which may play a role in the carcinogenesis induced by 1-NP. These data also suggest that individuals with impaired DNA repair enzymes might be more susceptible to lung cancer induced by 1-NP.
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