Nicotera T M, Block A W, Gibas Z, Sandberg A A
Mutat Res. 1985 Sep;151(2):263-8. doi: 10.1016/0027-5107(85)90078-8.
We have recently shown that Bloom syndrome fibroblasts have elevated levels of superoxide dismutase activity compared to those of normal fibroblasts. Based on this observation we decided to test whether an increased rate of superoxide radical production could be responsible for the induction of superoxide dismutase and of chromosomal aberrations and sister-chromatid exchanges characteristic of Bloom syndrome. Utilizing the superoxide-generating herbicide paraquat in Chinese hamster fibroblasts, we assayed the cells for dismutase activity, chromosomal aberrations and sister-chromatid exchanges. All 3 parameters investigated demonstrated a dose-dependent increase with paraquat and, consequently, with the superoxide produced. Since the induction of the enzyme is mediated by its substrate, the superoxide anion radical, we concluded that the increased dismutase activity (in Bloom syndrome and paraquat-treated cells) may be a secondary manifestation of an overall imbalance in oxygen metabolism and that this elevated enzymatic activity is insufficient to detoxify the high superoxide levels, which results in elevated levels of chromosomal damage.
我们最近发现，与正常成纤维细胞相比，布卢姆综合征成纤维细胞中超氧化物歧化酶活性水平升高。基于这一观察结果，我们决定测试超氧自由基产生速率的增加是否可能导致布卢姆综合征特有的超氧化物歧化酶的诱导以及染色体畸变和姐妹染色单体交换。在中国仓鼠成纤维细胞中使用产生超氧化物的除草剂百草枯，我们检测了细胞的歧化酶活性、染色体畸变和姐妹染色单体交换。所研究的所有三个参数均显示随着百草枯以及因此产生的超氧化物呈剂量依赖性增加。由于该酶的诱导是由其底物超氧阴离子自由基介导的，我们得出结论，（在布卢姆综合征和百草枯处理的细胞中）歧化酶活性增加可能是氧代谢总体失衡的次要表现，并且这种升高的酶活性不足以将高浓度的超氧化物解毒，从而导致染色体损伤水平升高。
