Gabrielson E W, Yu X Y, Spannhake E W
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Environ Health Perspect. 1994 Nov;102(11):972-4. doi: 10.1289/ehp.94102972.
In this study, we compared the cytotoxic and genotoxic effects of hydrogen peroxide and ozone on cultured human airway epithelial cells in primary culture. Both agents caused a dose-dependent loss in the replicative ability of epithelial cells and at higher levels of exposure caused acute cytotoxicity as measured by release of lactate dehydrogenase. Differences were seen, however, between the agents' effects with regard to induction of DNA single strand breaks as measured by alkaline elution:; whereas single-strand breaks were detected in significant amounts at concentration of hydrogen peroxide that cause acute cytotoxicity, none were detected at any of the levels of ozone exposure examined. A difference was also seen in the ability of the iron chelator deferoxamine to protect cells from the effect of the two oxidants. Preincubation of cultures with deferoxamine appreciably attenuated the toxicity of hydrogen peroxide but not of ozone. These data suggest that ozone has significant toxic effects on bronchial epithelial cells not mediated through the generation of hydrogen peroxide or hydroxyl radical. Furthermore, the data indicate that the inhibiting action of ozone on cell replicative ability is not mediated through a mechanism related to DNA single strand breaks.
在本研究中,我们比较了过氧化氢和臭氧对原代培养的人呼吸道上皮细胞的细胞毒性和遗传毒性作用。两种试剂均导致上皮细胞复制能力呈剂量依赖性丧失,且在较高暴露水平下,通过乳酸脱氢酶释放量测定显示出急性细胞毒性。然而,通过碱性洗脱法测定,在诱导DNA单链断裂方面,两种试剂的作用存在差异:在导致急性细胞毒性的过氧化氢浓度下可检测到大量单链断裂,而在所检测的任何臭氧暴露水平下均未检测到单链断裂。在铁螯合剂去铁胺保护细胞免受两种氧化剂作用的能力方面也存在差异。用去铁胺预孵育细胞培养物可显著减轻过氧化氢的毒性,但对臭氧则无此作用。这些数据表明,臭氧对支气管上皮细胞具有显著的毒性作用,且不是通过过氧化氢或羟基自由基的生成介导的。此外,数据表明臭氧对细胞复制能力的抑制作用不是通过与DNA单链断裂相关的机制介导的。