Chen J, Zhang Y, Sui J, Chen Y
Institute of Radiation Medicine, Beijing.
Chin Med Sci J. 1992 Dec;7(4):187-90.
The relationship between O6-methylguanine-DNA methyltransferase (O6-MT) activity and the sensitivity of 4 kinds of human tumor cell lines to bis-chloroethylnitrosourea (BCNU) was evaluated. The results demonstrated that cellular resistance to BCNU was linearly correlated with O6-MT activity, suggesting that O6-MT plays an important role in repairing DNA damage induced by BCNU. Furthermore, the depletion of O6-MT activity by streptozotocin (STZ) pretreatment and its effect on the cell's sensitivity to BCNU were investigated. O6-MT activity could be efficiently reduced, and sensitivity to BCNU was subsequently increased significantly. There was also a linear correlation between depletion of O6-MT activity and enhancement of BCNU's cytotoxic effects. These results indicate that O6-MT might constitute the molecular basis of cellular resistance to BCNU, and a combination of STZ and BCNU may result in better therapeutic effects.
评估了O6-甲基鸟嘌呤-DNA甲基转移酶（O6-MT）活性与4种人类肿瘤细胞系对双氯乙基亚硝脲（BCNU）敏感性之间的关系。结果表明，细胞对BCNU的耐药性与O6-MT活性呈线性相关，这表明O6-MT在修复BCNU诱导的DNA损伤中起重要作用。此外，研究了用链脲佐菌素（STZ）预处理对O6-MT活性的消耗及其对细胞对BCNU敏感性的影响。O6-MT活性可被有效降低，随后对BCNU的敏感性显著增加。O6-MT活性的消耗与BCNU细胞毒性作用的增强之间也存在线性相关。这些结果表明，O6-MT可能构成细胞对BCNU耐药的分子基础，STZ和BCNU联合使用可能产生更好的治疗效果。
