Spitz D R, Sim J E, Ridnour L A, Galoforo S S, Lee Y J
Section of Cancer Biology, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Ann N Y Acad Sci. 2000;899:349-62. doi: 10.1111/j.1749-6632.2000.tb06199.x.
Recently, glucose deprivation-induced oxidative stress has been shown to cause cytotoxicity, activation of signal transduction (i.e., ERK1, ERK2, JNK, and Lyn kinase), and increased expression of genes associated with malignancy (i.e., bFGF and c-Myc) in MCF-7/ADR human breast cancer cells. These results have led to the proposal that intracellular oxidation/reduction reactions involving hydroperoxides and thiols may provide a mechanistic link between metabolism, signal transduction, and gene expression in these human tumor cells. The current study shows that several other transformed human cell types appear to be more susceptible to glucose deprivation-induced cytotoxicity and oxidative stress than untransformed human cell types. In a matched pair of normal and SV40-transformed human fibroblasts the cytotoxic process is shown to be dependent upon ambient O2 concentration. A theoretical model to explain the results is presented and implications to unifying modern theories of cancer are discussed.
最近研究表明，葡萄糖剥夺诱导的氧化应激可导致MCF-7/ADR人乳腺癌细胞发生细胞毒性、信号转导激活（即细胞外调节蛋白激酶1、细胞外调节蛋白激酶2、应激活化蛋白激酶和Lyn激酶）以及与恶性肿瘤相关基因（即碱性成纤维细胞生长因子和原癌基因c-Myc）表达增加。这些结果提示，涉及氢过氧化物和硫醇的细胞内氧化/还原反应可能为这些人类肿瘤细胞的代谢、信号转导和基因表达之间提供一种机制联系。当前研究表明，与未转化的人类细胞类型相比，其他几种转化的人类细胞类型似乎对葡萄糖剥夺诱导的细胞毒性和氧化应激更敏感。在一对匹配的正常和SV40转化的人类成纤维细胞中，细胞毒性过程显示取决于周围的氧气浓度。本文提出了一个解释这些结果的理论模型，并讨论了其对统一现代癌症理论的意义。
