Changes in levels of 8-hydroxyguanine in DNA, its repair and OGG1 mRNA in rat lungs after intratracheal administration of diesel exhaust particles

Diesel exhaust particles (DEP), an environmental pollutant, are known to in duce lung cancer in experimental animals. To clarify whether reactive oxyge n species (ROS) are involved in its carcinogenic mechanism, we examined the levels of 8-hydroxyguanine (8-OH-Gua), its total repair and the repair enz yme OGG1 mRNA in female Fischer 344 rat lungs, as markers of the response t o ROS, after DEP was intratracheally instilled. The 8-OH-Gua levels in both DEP-treated groups (2 and 4 mg) were increased during the 2-8 h following exposure to DEP, The 8-OH-Gua repair activities in the DEP-treated groups d ecreased during the period from 2 h to 2 days following DEP exposure and th en recovered to the level of the control group at 5 days after exposure. OG G1 mRNA was induced in rats treated with 4 mg DEP for 5-7 days after admini stration. In conclusion, the 8-OH-Gua level in rat lung DNA increases marke dly at an early phase after DEP exposure, by the generation of ROS and the inhibition of 8-OH-Gua repair activity, and induction of OGG1 mRNA is also a good marker of cellular oxidative stress during carcinogenesis.