Contribution of nitrated polycyclic aromatic hydrocarbons in diesel particles to human lung cancer induction

By following the prognosis of 112 patients with carcinomas, we found that t he deposition of l-nitropyrene (1-NP), 1,3-dinitropylene (1,3-DNP), and 3-n itrofluoranthene (3-NF) in lung tissues influenced their 5-year-survival af ter determination of chemicals. Lung specimens were divided into two groups of higher and lower chemical concentrations at levels of 18 pg/g for 1-NP, 15 for 1,3-DNP, and 35 for 3-NF, and the findings were statistically analy zed by adjusting for age, gender, stage, smoking status and cell type. The 5-year-survival of patients was significantly lower in the higher concentra tion group than the lower group. In addition, the higher concentration grou p correlated significantly with poor cell differentiation. The results sugg est that tumors can be induced by continuous deposition of small amounts of environmental carcinogens in human lungs. Formation of 8-hydroxyguanosine (8-OHdG) is normally used as a biomarker of oxidative damage in in vitro and in vivo systems. 8-OHdG was detected in a ll 22 cases of lung tissues with carcinomas, and levels increased with the increasing age of the patients, suggesting a correlation between age and th e presence of diesel-originating carbon particles in lung tissues. In the i ntratracheal administration of diesel particles without most organic chemic als into mice, 8-OHdG formation was elevated more than by a single administ ration of benzo[a]pyrene, 1-NP and 1,8-DNP. These results suggest that carb oneceous particles, but not mutagens or carcinogens, promote the formation of 8-OHdG, and that as a mechanism, alveolar macrophages may be associated with oxidative damage, involving the generation of a hydroxyl radical durin g phagocytosis in the lungs.