Gerson S L, Willson J K
Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Hematol Oncol Clin North Am. 1995 Apr;9(2):431-50.
The DNA repair protein, O6-alkylguanine DNA alkyltransferase, is a major contributor to the resistance to the nitrosourea, triazine, and tetrazine class of alkylating agents. Many tumor cells and primary tumor samples contain high levels of this protein, although a great deal of heterogeneity exists between and within tumors. Inhibition of the alkyl-transferase by O6-benzylguanine results in significant potentiation of the cytotoxic effects of these chemotherapeutic agents, generating responses in human tumor xenografts that are completely resistant to nitrosoureas alone. These studies may rekindle the interest in the nitrosourea class of alkylating agents and stimulate the search for inhibitors of other mechanisms of chemotherapy resistance.
DNA修复蛋白O6-烷基鸟嘌呤DNA烷基转移酶是对亚硝基脲、三嗪和四嗪类烷化剂耐药的主要原因。许多肿瘤细胞和原发性肿瘤样本中该蛋白水平较高，不过肿瘤之间和肿瘤内部存在很大的异质性。O6-苄基鸟嘌呤对烷基转移酶的抑制作用可显著增强这些化疗药物的细胞毒性作用，在单独对亚硝基脲完全耐药的人肿瘤异种移植模型中产生反应。这些研究可能会重新激发人们对亚硝基脲类烷化剂的兴趣，并促使人们寻找其他化疗耐药机制的抑制剂。
