OXYGEN RADICALS IN LUNG CARCINOGENESIS ACCOMPANYING PHAGOCYTOSIS OF DIESEL EXHAUST PARTICLES

We sought to examine the involvement of oxygen radicals derived from p hagocytosis process in lung carcinogenesis induced by diesel exhaust p articles (DEP). The carcinogenic response and formation of 8-hydroxyde oxyguanosine (8-OHdG) were examined in the lungs of mice intratracheal ly injected with washed DEP (WDEP), DEP, or nontoxic control particles of titanium dioxide (TiO2). After 10 weekly treatments with these par ticles, the formation of 8-OHdG in the lungs of mice treated with WDEP or DEP showed a significant increase, but not in those treated with T iO2. After 12 months, the incidence of lung tumors in mice treated wit h WDEP or DEP was higher than that of mice treated with vehicle by 2.3 - and 3.1-fold, respectively. A significant difference in the incidenc e of tumors was found between the vehicle group and DEP-treated group. Treatment with TiO2 had no effect on the incidence of lung tumors. Th e formation of 8-OHdG in mice treated with these particles was signifi cantly correlated with the development of lung tumors. These results s uggest that the induction of DNA damage by oxygen radicals may be an i mportant factor in the initiation of WDEP- and DEP-induced lung carcin ogenesis, and that oxygen radicals derived from the phagocytic process may play a role in 8-OHdG formation induced by DEP.