Depletion of O6-methylguanine-DNA methyltransferase activity and potentiation of 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3 (2-chloroethyl)-3-nitro-sourea antitumor effect by streptozotocin

O 6 -methylguanine-DNA Methyltransferase (MGMT) can specifically repair the DNA demage induced by chloroethylnitrosoureas (CENU) such as 1-(4-amino-2-mcthja-pyrimidinyl) methyl- 3- (2- chloroethyl)- 3-nitrosourea (ACNU), constituting the molecular basis of tumor cell resistance to CENU. The present study demonstrated that sensitization of resistant tumor cells to ACNU could be achieved by streptozotocin (STZ) treatment which could deplete MGMT activity in vitro and in vivo . It suggested that depletion of the molecular basis of tumor cell resistance to chemotherapeutic agents might be a practicable way to improve the effectiveness of tumor chemotherapy.