Akman S A, Forrest G, Chu F F, Doroshow J H
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010.
Biochim Biophys Acta. 1989 Sep 21;1009(1):70-4. doi: 10.1016/0167-4781(89)90080-8.
We have established a variant of the human breast cancer cell line MCF7, designated MCF7/H2O2, which is 5-fold resistant to H2O2 by clonogenic assay. The specific activity of the H2O2 disposal enzyme catalase was elevated 3-fold in MCF7/H2O2; activities of other antioxidant enzymes, including glutathione peroxidase and superoxide dismutase, were not increased. The steady-state level of catalase mRNA was only slightly elevated (approx. 1.6-fold) in MCF7/H2O2 cells; however, degradation of catalase mRNA was markedly retarded in MCF-7/H2O2 compared to MCF-7 (82% of catalase mRNA remained 24 h after inhibition of RNA synthesis by actinomycin D in MCF-7/H2O2 vs. 32% in MCF7). The degradation rates of superoxide dismutase mRNA and 28 S ribosomal RNA were not reduced in MCF-7/H2O2; however, the rate of degradation of another mRNA species, beta-actin, was also significantly decreased. These data suggest that resistance to H2O2 in MCF7/H2O2 cells is mediated by elevated catalase activity which can be explained by stabilization of certain mRNA species, including catalase mRNA.
我们建立了人乳腺癌细胞系MCF7的一个变体，命名为MCF7/H2O2，通过克隆形成试验发现其对H2O2具有5倍的抗性。在MCF7/H2O2中，H2O2处理酶过氧化氢酶的比活性提高了3倍；其他抗氧化酶，包括谷胱甘肽过氧化物酶和超氧化物歧化酶的活性并未增加。在MCF7/H2O2细胞中，过氧化氢酶mRNA的稳态水平仅略有升高（约1.6倍）；然而，与MCF-7相比，MCF-7/H2O2中过氧化氢酶mRNA的降解明显延迟（在放线菌素D抑制RNA合成24小时后，MCF-7/H2O2中82%的过氧化氢酶mRNA仍然存在，而MCF7中为32%）。在MCF-7/H2O2中，超氧化物歧化酶mRNA和28 S核糖体RNA的降解速率并未降低；然而，另一种mRNA，β-肌动蛋白的降解速率也显著降低。这些数据表明，MCF7/H2O2细胞对H2O2的抗性是由过氧化氢酶活性升高介导的，这可以通过包括过氧化氢酶mRNA在内的某些mRNA种类的稳定来解释。
