CONCENTRATION-DEPENDENT AND TIME-DEPENDENT FORMATION OF DNA ADDUCTS IN LUNGS OF RATS EXPOSED TO DIESEL EXHAUST
CONCENTRATION-DEPENDENT AND TIME-DEPENDENT FORMATION OF DNA ADDUCTS IN LUNGS OF RATS EXPOSED TO DIESEL EXHAUST
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DOI：
10.1016/0300-483x(90)90167-f
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发表时间：
1990-01-01
期刊：
影响因子：
4.5
通讯作者：
WOLFF, RK
中科院分区：
文献类型：
--
作者：
BOND, JA;MAUDERLY, JL;WOLFF, RK
柴油废气(DE)是啮齿动物的一种肺部致癌物质。先前的研究表明，在大鼠暴露于高浓度(10毫克煤烟/立方米)DE后，可以在肺组织中测量到DNA加合物。本研究的目的是研究DE暴露12周后肺DNA加合物的形成和耐受的动力学特征，并确定加合物形成的暴露浓度的影响。将大鼠暴露于过滤空气(对照组)或稀释DE(0.35-10 mg烟尘/立方米)中，每天7小时，每周5天，持续12周。用~(32)P-后标记法分析大鼠肺DNA中DNA加合物的存在。暴露在不同尾气浓度下的大鼠肺内DNA加合物水平相似，约为对照组的两倍(.apprx。14对7加合物/109个碱基)。对照组大鼠肺中的DNA加合物水平在暴露12周期间保持相对恒定。相比之下，暴露在DE烟尘中的大鼠肺DNA加合物水平在暴露12周期间缓慢积累，并在暴露结束时达到最高。DNA加合物水平在停止接触后迅速下降。由于肺部中的加合物水平在所研究的所有浓度下都是相似的，并且发现在不显著增加肿瘤发病率的暴露水平(0.35毫克烟尘/立方米)下，大鼠的加合物增加，因此很可能除了肺DNA加合物的形成之外，因素必须参与DE诱导的致癌性。我们的结论是，煤烟相关有机化合物的代谢产物形成肺DNA加合物可能只是DE诱发肺癌发生的一个步骤。
Diesel exhaust (DE) is a pulmonary carcinogen in rodent. Previous studies have demonstrated that following exposure of rats to high concentrations (10 mg soot/m3) of DE, DNA adducts can be measured in lung tissue. The purpose of the present study was to characterize the kinetics of formation and persistance of lung DNA adducts after a 12-week exposure to DE and to determine the effect of exposure concentration of adduct formation. Rats were exposed for 7 h/day, 5 days/week, for up to 12 weeks, to filtered air (controls) or to diluted DE (0.35-10 mg soot/m3). DNA from lungs of rats was analyzed for the presence of DNA adducts by the 32P-postlabeling method. Levels of DNA adducts in lungs of rats exposed to be different exhaust concentrations were similar, and were about twice control values (.apprx. 14 vs. 7 adducts/109 bases). DNA adduct levels in lungs of control rats remained relatively constant throughout the 12-week exposure period. In contrast, lung DNA adduct levels in rats exposed to DE soot accumulated slowly during the 12-week exposure, and were highest at the end of exposure. DNA adduct levels declined rapidly after the termination of exposure. Because adduct levels in lungs were similar at all concentrations examined and the finding that adducts were increased in rats at an exposure level that does not significantly increase tumor incidence (0.35 mg soot/m3), it is likely that factors in addition to lung DNA adduct formation must be involved in DE-induced carcinogenicity. We concluded that the formation of lung DNA adducts by metabolites of soot-associated organic compounds may be only one step in the initiation of DE-induced pulmonary carcinogenesis.