Early Oxidative DNA Damages and Late Development of Lung Cancer in Diesel Exhaust-Exposed Rats

• Published in: Environmental research Vol. 84; no. 3; pp. 255 - 264
• Main Authors: Iwai, Kazuro, Adachi, Shuichi, Takahashi, Mihoko, Möller, Lennart, Udagawa, Tadashi, Mizuno, Satoru, Sugawara, Isamu
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier Inc 01.11.2000; Elsevier
• Subjects: 8-hydroxy-deoxyguanosine; Air; Animals; Biological and medical sciences; Cell Transformation, Neoplastic; diesel; diesel exhaust; DNA adduct; DNA Adducts; DNA Damage; Environmental pollutants toxicology; Female; Inhalation Exposure; lung cancer; Lung Neoplasms - chemically induced; Lung Neoplasms - pathology; Medical sciences; Medicin och hälsovetenskap; Oxidative Stress; Rats; Time Factors; Toxicology; Vehicle Emissions - adverse effects; lung cancer; DNA adduct; 8-hydroxy-deoxyguanosine; diesel exhaust; inhalation exposure; Lung disease; Rat; Respiratory disease; Diesel fuel; Toxicity; Rodentia; Tumorigenicity; Malignant tumor; Bronchopulmonary; Inhalation; Carcinogen; Vertebrata; Chronic; Mammalia; Histopathology; Animal; DNA; Bronchus disease; Exhaust gas; Lesion; Molecular adduct
• ISSN: 0013-9351; 1096-0953
• DOI: 10.1006/enrs.2000.4072

To demonstrate DNA damages in the early stage of diesel exhaust exposure, an inhalation study of 1 through 12 months was conducted. The lung burden of diesel soot increased with increase in exposure duration. Histologically, hyperplastic foci of alveolar epithelia were found at 6-month exposure and became prominent at the 12th month, with slight nuclear atypia and positive p53 staining. The level of 8-OH-hydroxyguanosine (8-OH-dG) in the exposed rat lungs showed an increase from 1 month of exposure, followed by a gradual increase, reaching almost a plateau level at the 9th month. An in vitro experiment demonstrated significant 8-OH-dG formation when diesel particles and H2O2 were added to the DNA solution. The level of bulky aromatic DNA adducts peaked at the 1st month of exposure, followed by a decrease. By the end of the observation period of 30 months, lung tumors developed even in the 6-month exposure group, and the earliest lung tumors were found only in rats that survived longer than 18 months. In conclusion, persisting oxidative stress on DNA induced in the early phase of diesel exhaust exposure, together with inflammation, seems to play an important role in carcinogenesis at advance ages after a long latent period.