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.