8-Hydroxyguanosine formed in human lung tissues and the association with diesel exhaust particles.

Diesel exhaust particles consist of various organic chemicals, heavy metals, and carbon particles. Knowledge of the fate of organic chemicals and carbon particles in the lungs is important to determine the mechanisms responsible for lung tumors. In the present study, diesel particle extracts were found to show mutagenicity for YG3003, a sensitive strain to some oxidative mutagens, as well as other mutant strains, and those of lung tissues obtained from lung cancer patients exhibited potent mutagenicity. Formation of 8-hydroxyguanosine (8-OHdG) as a biomarker of oxidative damage was analyzed with in vitro and in vivo assay systems. The 8-OHdG was detected in all 22 cases of lung tissues with carcinomas tested and their levels increased with the increasing age of the patients, suggesting a correlation between age and the presence of carbon particles in lung tissues. Therefore, the formation of 8-OHdG due to diesel exhaust particles was investigated via intratracheal injections into mice. 8-OHdG formation was elevated when carboneceous particles, after removal of organic chemicals with various solvents, were administered to mice, but it was not elevated when polyaromatic compounds such as benzo[a]pyrene, 1,8-dinitropyrene, and 1-nitropyrene were used in the same procedure in mice. The carboneceous particles were formed from a giant particle that was aggregated by micro-particles with diameters of 1.47 +/- 1.34 to 1.05 +/- 0.83 microm. These results suggest that carboneceous particles, but not mutagens and carcinogens, promote the formation of 8-OHdG, and that as a mechanism, alveolar macrophages may be involved in oxidative damage. The oxidative damage may be due to the fact that the mutation is involved with the generation of a hydroxyl radical during phagocytosis, and the hydroxyl radical leads to hydroxylation at the C-8 position of the deoxyguanosine residue in the DNA.