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 carb on particles in the lungs is important to determine the mechanisms responsi ble for lung tumors. In the present study, diesel particle extracts were fo und to show mutagenicity for YG3003, a sensitive strain to some oxidative m utagens, as well as other mutant strains, and those of lung tissues obtaine d from lung cancer patients exhibited potent mutagenicity. Formation of 8-h ydroxyguanosine (8-OHdG) as a biomarker of oxidative damage was analyzed wi th in vitro and in vivo assay systems. The 8-OHdG was detected in all 22 ca ses of lung tissues with carcinomas tested and their levels increased with the increasing age of the patients, suggesting a correlation between age an d the presence of carbon particles in lung tissues. Therefore, the formatio n of 8-OHdC due to diesel exhaust particles was investigated via intratrach eal injections into mice. 8-OHdG formation was elevated when carboneceous p articles, after removal of organic chemicals with various solvents, were ad ministered to mice, but it was not elevated when polyaromatic compounds suc h as benzo[a]pyrene, 1,8-dinitropyrene, and I-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 mu m. These results suggest that carboneceous partic les, but not mutagens and carcinogens, promote the formation of 8-OHdG, and that as a mechanism, alveolar macrophages may be involved in oxidative dam age. The oxidative damage may be due to the fact that the mutation is invol ved with the generation of a hydroxyl radical during phagocytosis, and the hydroxyl radical leads to hydroxylation at the C-8 position of the deoxygua nosine residue in the DNA. (C) 1999 Elsevier Science Inc.