LUNG CARCINOGENESIS AND FORMATION OF 8-HYDROXY-DEOXYGUANOSINE IN MICEBY DIESEL EXHAUST PARTICLES

In order to clarify the involvement of oxygen radicals in lung carcino genesis induced by diesel exhaust particles (DEP), the relationship be tween lung tumour response and formation of 8-hydroxydeoxyguanosine (8 -OHdG) in lung DNA was examined. The role of high dietary fat and beta -carotene on these responses was also studied. Mice were intratracheal ly injected with 0.05, 0.1 and 0.2 mg of DEP per animal once weekly fo r 10 weeks. After 12 months, the lung tumour incidence in mice treated with 0.05 mg and 0.1 mg showed similar increases (30% and 31%), but w as decreased to 24% at 0.2 mg. High dietary fat enhanced the incidence of both benign and malignant tumours, beta-carotene partially prevent ed the tumour development. After the 10 weekly treatments of DEP, infl ammatory reaction was observed in the respiratory tract and alveoli. T he formation of 8-OHdG in lung DNA from mice treated with DEP showed a dose dependent increase. 8-OHdG formation was enhanced by high dietar y fat and partially reduced by beta-carotene. Formation of 8-OHdG was significantly correlated with the lung tumour incidence except at 0.2 mg. These results suggest that the induction of oxidative DNA damage m ay be an important factor in the initiation of DEP-induced lung carcin ogenesis, and that beta-carotene and high dietary fat may play a role in the regulation of tumour development via modulation of the formatio n of 8-OHdG.