O6-methylguanine-DNA methyltransferase activity and sensitivity of human tumor cell lines to bis-chloroethylnitrosourea.
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.
Chen
J
J
Institute of Radiation Medicine, Beijing.
Zhang
Y
Y
Sui
J
J
Chen
Y
Y
D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D002330:Carmustine / Q000494:pharmacology*; D004351:Drug Resistance; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D008780:Methyltransferases / Q000378:metabolism*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D013311:Streptozocin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology
D013311:Streptozocin; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D002330:Carmustine