RADIOSENSITIZATION OF AERATED AND HYPOXIC MAMMALIAN CELLS

本研究的一个主要部分涉及的重要性， 细胞氧化还原系统如谷胱甘肽（GSH）和相关的 酶对细胞抵抗电离辐射的防御作用， 化疗药物 最近的研究清楚地表明， 固有的GSH水平并没有显着有助于 辐射反应 我们的工作证实了这一说法 使用导致GSH耗竭至对照组<5%的药物，或 提升至2倍。 在这些条件下，放射敏感性是 影响不大（约10%）。 最近用一种变异的CHO 细胞系，发现放射敏感性与 亲本细胞系，尽管突变细胞系具有 GSH水平高2倍。 顺便说一句，这种突变细胞系是 对多种化疗药物有明显耐药性。 因此，在本发明中， 未发现与化学抗性和放射敏感性的联系。 GSH调节被发现显著改变化疗 特别是对美法仑和顺铂等药物的反应。 特别注意的是， 自动化药物敏感性（MTT测定）以筛选大组（30 细胞系）的人肺癌细胞系，以确定 化疗敏感性与GSH水平之间存在相关性。 基本上，结果表明，细胞系（小细胞）低， GSH对顺铂、美法仑、阿霉素敏感 GSH比细胞系高2-3倍（非小细胞）。 的 观察到的化学敏感性模式与所观察到的 临床上 这些研究需要进一步调查， 使用GSH水平作为肿瘤反应预测因子的可能性 化疗药物。

A major portion of this study has dealt with the importance of cellular redox systems such as glutathione (GSH) and related enzymes to the cell's defense against ionizing radiation and chemotherapy drugs. Recent studies have clearly shown that inherent GSH levels do not significantly contribute to the radiation response. This statement is substantiated by our work using drugs that result in GSH depletion to <5% of control or elevation to 2 fold. Under these conditions, radiosensitivity was affected modestly (approximately 10%). Recently using a mutant CHO cell line, radiosensitivity was found to be identical to the parental cell line, despite the fact that the mutant cell line has GSH levels 2 fold higher. Incidentally, this mutant cell line was markedly resistant to a wide variety of chemotherapy drugs. Thus, a link with chemoresistance and radiosensitivity was not found. GSH modulation was found to significantly alter the chemotherapy response particularly for drugs such as melphalan and cisplatin. Particular attention was directed toward the development of an automated drug sensitivity (MTT assay) to screen a large panel (30 cell lines) of human lung cancer lines to determine if a relationship between chemosensitivity and GSH levels exists. Basically, the results showed that cell lines (small cell) low in GSH were more sensitive to cisplatin, melphalan, and adriamycin than cell lines 2-3 fold higher in GSH (non-small cell). The patterns of chemosensitivity observed correlated with what is seen clinically. These studies warrant further investigation as to the possibility of using GSH levels as a predictor of tumor response to chemotherapy drugs.