Lung carcinogenesis and formation of 8-hydroxy-deoxyguanosine in mice by diesel exhaust particles.

Abstract

In order to clarify the involvement of oxygen radicals in lung carcinogenesis induced by diesel exhaust particles (DEP), the relationship between 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 intratracheally injected with 0.05, 0.1 and 0.2 mg of DEP per animal once weekly for 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 was decreased to 24% at 0.2 mg. High dietary fat enhanced the incidence of both benign and malignant tumours. beta-carotene partially prevented the tumour development. After the 10 weekly treatments of DEP, inflammatory reaction was observed in the respiratory tract and alveoli. The formation of 8-OHdG in lung DNA from mice treated with DEP showed a dose dependent increase. 8-OHdG formation was enhanced by high dietary 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 may be an important factor in the initiation of DEP-induced lung carcinogenesis, and that beta-carotene and high dietary fat may play a role in the regulation of tumour development via modulation of the formation of 8-OHdG.