Lung carcinogenesis by diesel exhaust particles and the carcinogenic mechanism via active oxygens

In an experiment to clarify the involvement of oxygen radicals in icing car cinogenesis induced by diesel exhaust particles (DEP), Ive found that there is a strong relation between lung tumor response and formation of 8-hydrox ydeoxyguanosine (8-OHdG) in lung DNA of mice administered DEP by repeated i ntratracheal instillation. Repealed intratracheal instillation of DEP also induced the activity of cytochrome P-450 reductase in the lungs as a repres entative enzyme of superoxide generation, and two types or nitric oxide (NO ) synthase, cNOS and iNOS, in the lungs. On the other hand, activities of C uZn-superoxide dismutase (SOD) and Mn-SOD antioxidant enzymes were depresse d by the instillation of DEP. These results suggest that generation of supe roxide, hydroxyl radical, and nitric oxide are increased in epithelial cell s in airways, and that the increased superoxide and nitric oxide react very easily to produce peroxynitrite (ONOO-). The peroxynitrite also produce hy droxyl radical. The hydroxyl radical may play an important role in carcinog enesis by DEP.