TY - JOUR T1 - Investigation of Cell Death Induced by <em>N</em>-Methyl-<em>N</em>-Nitrosourea in Cell Lines of Human Origin and Implication of RNA Binding Protein Alterations JF - Anticancer Research JO - Anticancer Res SP - 4291 LP - 4299 VL - 31 IS - 12 AU - A. KORYLLOU AU - M. PATRINOU-GEORGOULA AU - A. DIMOZI AU - S.A. KYRTOPOULOS AU - V. PLETSA Y1 - 2011/12/01 UR - http://ar.iiarjournals.org/content/31/12/4291.abstract N2 - Methylating agents, a widely used class of anticancer drugs, induce DNA methylation adducts, the most biologically significant being O6-methylguanine. The efficacy of these drugs depends on the interplay of three DNA repair systems: base excision repair (BER), methyl-directed mismatch repair (MMR) and direct damage reversal by O6-methylguanine-DNA methyltransferase (MGMT). An MGMT-inducible, MMR- and BER-proficient HeLa cell line was treated with different concentrations of N-methyl-N-nitrosourea (MNU), a model SN1 methylating agent, analogous to widely used methylating cancer chemotherapeutic drugs, under different expression levels of the repair enzyme (MGMT). MNU induced MGMT-dependent apoptotic cell death. In this particular cellular context, the induction of apoptosis was accompanied by modifications of the RNA binding protein poly(A)polymerase and significant down-regulation of the heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2. These results implicate alterations of the above mentioned RNA binding proteins in SN1 methylating agent-induced cell death and apoptosis, providing a possible perspective regarding their use as biomarkers of tumor resistance/sensitivity to chemotherapy. ER -