An J, Hsie A W
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77550.
Mutat Res. 1992 Nov 16;270(2):167-75. doi: 10.1016/0027-5107(92)90127-n.
We have investigated the roles of reactive oxygen species (ROS) in bleomycin (BLM)-induced gene mutations in Chinese hamster ovary (CHO) cells using a superoxide dismutase (SOD) inhibitor, triethylenetetramine (TRIEN), and a SOD mimic, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEM-POL), to lower and increase intracellular 'SOD activity', respectively. Pretreatment of CHO cells with TRIEN (1 mM) for 1 h enhanced the mutagenic response of BLM (5-50 micrograms/ml, 1 h treatment) in the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus in CHO cell clone K1-BH4 (CHO/HPRT assay) and the xanthine-guanine phosphoribosyltransferase (gpt) gene in a CHO-K1 cell derivative AS52 (AS52/GPT assay). Pretreatment with TEMPOL (1 mM) for 1 h decreased the BLM (20-100 micrograms/ml, 1 h treatment) mutagenicity in the AS52/GPT assay. The mutagenic response of BLM appears to be modulated by the intracellular level of 'SOD activity' and hence the intracellular level of ROS. These data provide further evidence for the involvement of ROS in bleomycin mutagenesis in mammalian cells.
我们使用超氧化物歧化酶（SOD）抑制剂三亚乙基四胺（TRIEN）和SOD模拟物4-羟基-2,2,6,6-四甲基哌啶-1-氧基（TEM-POL），分别降低和提高细胞内“SOD活性”，研究了活性氧（ROS）在中国仓鼠卵巢（CHO）细胞中博来霉素（BLM）诱导基因突变中的作用。用TRIEN（1 mM）预处理CHO细胞1小时，增强了BLM（5-50微克/毫升，处理1小时）在CHO细胞克隆K1-BH4的次黄嘌呤-鸟嘌呤磷酸核糖转移酶（hprt）位点（CHO/HPRT检测）和CHO-K1细胞衍生物AS52（AS52/GPT检测）中的黄嘌呤-鸟嘌呤磷酸核糖转移酶（gpt）基因的诱变反应。用TEMPOL（1 mM）预处理1小时，降低了BLM（20-100微克/毫升，处理1小时）在AS52/GPT检测中的致突变性。BLM的诱变反应似乎受细胞内“SOD活性”水平以及因此受细胞内ROS水平的调节。这些数据为ROS参与哺乳动物细胞中博来霉素诱变提供了进一步的证据。
