The effects of 1-nitropyrene on oxidative DNA damage and expression of DNA repair enzymes.
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.
Kim
Yong-Dae
YD
Department of Preventive Medicine & Medical Research Center, College of Medicine, Chungbuk National University, South Korea.
Ko
Young-Jun
YJ
Kawamoto
Toshihiro
T
Kim
Heon
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D018929:Cell Culture Techniques; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000139:chemically induced; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D011721:Pyrenes / Q000633:toxicity*
D009153:Mutagens; D011721:Pyrenes; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045643:DNA Repair Enzymes; D003849:Deoxyguanosine; C032668:1-nitropyrene