Mattern J, Eichhorn U, Kaina B, Volm M
Department of Oncological Diagnostics and Therapy, German Cancer Research Center, Heidelberg.
Int J Cancer. 1998 Sep 11;77(6):919-22. doi: 10.1002/(sici)1097-0215(19980911)77:6<919::aid-ijc20>3.0.co;2-v.
The DNA repair protein O6-methylguanine-DNA methyl-transferase (MGMT) is a main determinant of resistance of cells to the cytostatic effects of O6-alkylguanine-generating alkylating agents. The purpose of our study was to assay MGMT activity in cells of lung cancers and to correlate MGMT levels with chemotherapy response to cyclophosphamide (CTX) and cisplatin (DDP). MGMT levels were determined in 14 human lung tumor xenografts. There was a wide variation of MGMT expression in these tumors, ranging from 10 to 984 fmol/mg protein. There was also a wide range in the sensitivity of the xenografts to CTX and DDP, as measured by specific growth delay. When the MGMT levels of the different xenograft lines were compared with the corresponding responses to CTX and DDP, a close correlation was found between MGMT activity and CTX (lin reg., r = -0.83, p < 0.05). The higher the MGMT activity, the less pronounced was the growth-inhibiting effect of CTX. With DDP, no such correlation was found. Our results indicate that the in vivo response of tumors to CTX is related to the level of MGMT expression.
DNA修复蛋白O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）是细胞对产生O6-烷基鸟嘌呤的烷化剂细胞抑制作用耐药性的主要决定因素。我们研究的目的是检测肺癌细胞中的MGMT活性，并将MGMT水平与对环磷酰胺（CTX）和顺铂（DDP）的化疗反应相关联。在14个人类肺肿瘤异种移植模型中测定了MGMT水平。这些肿瘤中MGMT表达存在广泛差异，范围为10至984 fmol/mg蛋白质。通过特定生长延迟测量，异种移植模型对CTX和DDP的敏感性也存在广泛差异。当比较不同异种移植系的MGMT水平与对CTX和DDP的相应反应时，发现MGMT活性与CTX之间存在密切相关性（线性回归，r = -0.83，p < 0.05）。MGMT活性越高，CTX的生长抑制作用越不明显。对于DDP，未发现这种相关性。我们的结果表明，肿瘤对CTX的体内反应与MGMT表达水平有关。
