Hussain M Z, Mustafa M G, Ghani Q P, Bhatnagar R S
Arch Biochem Biophys. 1985 Sep;241(2):477-85. doi: 10.1016/0003-9861(85)90573-9.
Toxic effects of O3 are mediated through the formation of free radicals, which can cause DNA strand breaks. Cellular DNA repair is dependent upon the formation of poly(ADP-ribose) (polyADPR) catalyzed by polyADPR synthetase. In order to evaluate whether O3 exposure inflicted DNA damage in lung tissue, we measured the activity of polyADPR synthetase (known to be activated in response to DNA damage) in mouse lungs after exposure to 0.45 ppm (882 micrograms/m3) O3 for up to 7 days. The enzyme activity was stimulated with O3 exposure relative to unexposed controls, showing a 20% (P less than 0.05) increase at Day 5 and 42% (P less than 0.001) at Day 7 of O3 exposure. In addition, the activity of superoxide dismutase (SOD), known to be stimulated in response to production of superoxide anion (.O2-), was measured as an indicator of free radical involvement. Relative to unexposed controls, the SOD activity in exposed animal lungs increased to the peak level at Day 5 (48%, P less than 0.001) and then declined at Day 7 of O3 exposure but was still higher than controls (17%, P less than 0.05). When animals, after 5 days of O3 exposure, were allowed to recover in filtered room air, the activities of both enzymes declined to their respective control values in 6 days. These results suggest a possible temporal relationship between O3 injury and the activities of polyADPR synthetase and a free radical scavenging enzyme, SOD. The stimulation of polyADPR synthetase activity with O3 exposure, reflecting a response to lung cellular DNA repair, may be a sensitive indicator for assessing DNA damage in oxidant injury.
臭氧（O3）的毒性作用是通过自由基的形成介导的，自由基可导致DNA链断裂。细胞DNA修复依赖于由聚（ADP-核糖）合成酶催化形成的聚（ADP-核糖）（polyADPR）。为了评估臭氧暴露是否会对肺组织造成DNA损伤，我们在小鼠暴露于0.45 ppm（882微克/立方米）的臭氧长达7天后，测量了小鼠肺中聚（ADP-核糖）合成酶（已知在DNA损伤时被激活）的活性。与未暴露的对照组相比，臭氧暴露会刺激该酶的活性，在臭氧暴露第5天增加了20%（P<0.05），在第7天增加了42%（P<0.001）。此外，作为自由基参与指标，测量了已知会因超氧阴离子（·O2-）产生而被刺激的超氧化物歧化酶（SOD）的活性。与未暴露的对照组相比，暴露动物肺中的SOD活性在第5天增加到峰值水平（48%，P<0.001），然后在臭氧暴露第7天下降，但仍高于对照组（17%，P<0.05）。当动物在臭氧暴露5天后，置于过滤后的室内空气中恢复时，两种酶的活性在6天内均降至各自的对照值。这些结果表明，臭氧损伤与聚（ADP-核糖）合成酶和自由基清除酶SOD的活性之间可能存在时间关系。臭氧暴露刺激聚（ADP-核糖）合成酶活性，反映了对肺细胞DNA修复的反应，可能是评估氧化损伤中DNA损伤的敏感指标。
