The effects of 1-nitropyrene on oxidative DNA damage and expression of DNA repair enzymes

J Occup Health. 2005 May;47(3):261-6. doi: 10.1539/joh.47.261.

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.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Cell Culture Techniques
  • Cell Line
  • DNA Damage / drug effects*
  • DNA Repair Enzymes / metabolism*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / biosynthesis
  • Humans
  • Japan
  • Lung Neoplasms / chemically induced
  • Mutagens / toxicity*
  • Oxidative Stress / drug effects*
  • Pyrenes / toxicity*

Substances

  • Mutagens
  • Pyrenes
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA Repair Enzymes
  • Deoxyguanosine
  • 1-nitropyrene