O6-methylguanine-DNA methyltransferase activity and sensitivity of human tumor cell lines to bis-chloroethylnitrosourea

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / pathology
  • Carmustine / pharmacology*
  • Drug Resistance
  • Drug Synergism
  • Female
  • Humans
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / pathology
  • Methyltransferases / metabolism*
  • O(6)-Methylguanine-DNA Methyltransferase
  • Streptozocin / pharmacology
  • Tumor Cells, Cultured / drug effects
  • Tumor Stem Cell Assay
  • Uterine Cervical Neoplasms / enzymology*
  • Uterine Cervical Neoplasms / pathology


  • Streptozocin
  • Methyltransferases
  • O(6)-Methylguanine-DNA Methyltransferase
  • Carmustine