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BACKGROUND/AIM Temozolomide (TMZ) induces prolonged arrest of human glioma cells in the G2/M phase and inhibition of the G2 checkpoint intensifies the effect of TMZ. These findings suggest that the G2 checkpoint is linked to DNA repair mechanisms. MATERIALS AND METHODS To clarify the mechanism of TMZ resistance, we established TMZ-resistant (TR) clones by serial treatment of U87MG cells with TMZ. We evaluated TMZ-induced cell cycle arrest and the effect of various G2 checkpoint inhibitors. RESULTS We observed that longer exposure (over