Hotta T, Saito Y, Fujita H, Mikami T, Kurisu K, Kiya K, Uozumi T, Isowa G, Ishizaki K, Ikenaga M
Department of Neurosurgery, Hiroshima University School of Medicine, Japan.
J Neurooncol. 1994;21(2):135-40. doi: 10.1007/BF01052897.
Activity of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) is an important determinant of responsiveness of tumor cells to chloroethylnitrosoureas (CENUs), representative chemotherapeutic agents for primary malignant gliomas. In order to assess the real states of this repair protein in human malignant gliomas, we assayed AGT activity in surgically extirpated 42 malignant glioma samples and studied the distribution of the activity under certain clinical conditions. There were wide variations in AGT activity between individuals. No significant difference in AGT activity on average was seen either between glioblastoma and anaplastic astrocytoma, nor between primary and recurrent tumors. Among 42 malignant gliomas, 7 samples (16.7%) had low AGT activity less than 0.1 pmoles/mg protein. In the case of glioblastoma, tumors possessing higher AGT activity tended to be less responsive to post-operation remission-induction therapy including CENUs. The result of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) chemosensitivity assay by using the corresponding surgical specimens suggested a close relationship between cellular resistance to CENUs and AGT activity. It was found to be unlikely that a short term administration of CENUs had a significant effect on AGT activity of brain tumors in human body. We could detect a bit of definite evidences of the relevance of AGT to resistance to CENUs and need to conduct further investigations for other resistance factors.
DNA修复蛋白O6-烷基鸟嘌呤-DNA烷基转移酶（AGT）的活性是肿瘤细胞对氯乙基亚硝脲（CENUs）反应性的重要决定因素，CENUs是原发性恶性胶质瘤的代表性化疗药物。为了评估这种修复蛋白在人类恶性胶质瘤中的实际状态，我们检测了42例手术切除的恶性胶质瘤样本中的AGT活性，并研究了在特定临床条件下该活性的分布情况。个体之间的AGT活性存在很大差异。胶质母细胞瘤和间变性星形细胞瘤之间，以及原发性肿瘤和复发性肿瘤之间，AGT活性平均无显著差异。在42例恶性胶质瘤中，7个样本（16.7%）的AGT活性较低，低于0.1皮摩尔/毫克蛋白质。在胶质母细胞瘤病例中，AGT活性较高的肿瘤对包括CENUs在内的术后缓解诱导治疗的反应往往较小。使用相应手术标本进行的3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）化学敏感性试验结果表明，细胞对CENUs的耐药性与AGT活性密切相关。发现短期给予CENUs对人体脑肿瘤的AGT活性不太可能有显著影响。我们能够检测到一些AGT与对CENUs耐药性相关的确切证据，并且需要对其他耐药因素进行进一步研究。
