Iwai K, Adachi S, Takahashi M, Möller L, Udagawa T, Mizuno S, Sugawara I
Research Institute of Tuberculosis, Japan Anti-TB Association, 3-1-24, Matsuyama, Kiyose, Tokyo 204-0022, Japan.
Environ Res. 2000 Nov;84(3):255-64. 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 H(2)O(2) 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.
为了证明柴油废气暴露早期的DNA损伤，进行了为期1至12个月的吸入研究。柴油烟尘在肺内的沉积量随暴露时间的增加而增加。组织学上，在暴露6个月时发现肺泡上皮细胞增生灶，在第12个月时变得明显，伴有轻微核异型性和p53染色阳性。暴露大鼠肺中8-羟基鸟苷（8-OH-dG）水平从暴露1个月起开始升高，随后逐渐上升，在第9个月时几乎达到平台期。体外实验表明，当向DNA溶液中加入柴油颗粒和H2O2时，会有显著的8-OH-dG形成。大分子芳香族DNA加合物水平在暴露第1个月时达到峰值，随后下降。到30个月观察期结束时，即使是6个月暴露组也出现了肺肿瘤，最早的肺肿瘤仅在存活超过18个月的大鼠中发现。总之，柴油废气暴露早期诱导的DNA持续氧化应激与炎症一起，似乎在长期潜伏期后的老年期致癌过程中起重要作用。
