MGMT contributes to glioma cell line alkylator resistance

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Ablation of O6-methylguanine-DNA methyltransferase (MGMT) activity wih O6-benzylguanine in potentiates sensitivity to temozolomide and BCNU in human glioma cell lines. Analysis of 9 MGMT-expressing human gliomas revealed that treatment with O6-benzylguanine reduced the drug dose required to reduce survival of colony-forming ability to 10% (LD10) an average of 2.0-fold for BCNU, ranging from no increase for 2 lines to 2.7-fold. In contrast, the mean reduction of LD10 for temozolomide was 8.5-fold, ranging from 2- to 20-fold. Potentiation of alkylator cytotoxicity by ablation of MGMT is illustrated above for SF767. Our results document the contribution of MGMT to alkylator resistance in glioma cells.