O6-alkylguanine DNA-alkyltransferase is not a major determinant of sensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea in four medulloblastoma cell lines

Oncol Res. 1992;4(6):241-8.


The protein O6-alkylguanine-DNA alkyltransferase (O6-AGT) has been implicated as a major determinant of resistance of diverse tumors to chloroethylnitrosoureas. To evaluate the contribution of O6-AGT to resistance of medulloblastomas to chloroethylnitrosoureas, we assessed the role of O6-AGT in determining (BCNU). Sensitivity to BCNU cytotoxicity, measured as dose dependent survival of soft agar colony forming ability, varied among the lines. Two lines (UW443 and UW228-3) displayed linear survival curves and comparable BCNU sensitivity (D37 ca. 140 microM). The other lines (UW228-2 and UW228-1) had biphasic survival curves indicating that each line was composed of two sub-populations that differed in BCNU sensitivity. The D37 for these sub-populations ranged from 51 microM to 253 microM. The O6-AGT activities of the cell lines, however, did not reflect their varied susceptibilities to BCNU as evidenced by a 9-fold difference in O6-AGT activity between UW443 and UW228-3. Moreover, elimination of O6-AGT activity by the inhibitor O6-benzylguanine did not appreciably increase sensitivity to BCNU compared with the response of other human tumor cells [Dolan et al. Cancer Res. 51:3367-3372, 1991]. Our results demonstrate that O6-AGT is not a major determinant of BCNU sensitivity in the four medulloblastoma lines.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carmustine / metabolism
  • Carmustine / pharmacology*
  • Cell Survival
  • Cerebellar Neoplasms / metabolism*
  • Drug Resistance
  • Guanine / analogs & derivatives*
  • Guanine / pharmacology
  • Humans
  • Medulloblastoma / metabolism*
  • Methyltransferases / antagonists & inhibitors
  • Methyltransferases / metabolism*
  • O(6)-Methylguanine-DNA Methyltransferase
  • Tumor Cells, Cultured


  • O(6)-benzylguanine
  • Guanine
  • Methyltransferases
  • O(6)-Methylguanine-DNA Methyltransferase
  • Carmustine