APOPTOSIS INDUCED BY MICROTUBULE DISRUPTING DRUGS IN NORMAL MURINE THYMOCYTES IN-VITRO

Disruption of cytoplasmic and spindle microtubules by colchicine or no codazole increases mitotic index, but it also enhances apoptosis in is olated mouse thymocytes; the apoptotic index exceeds 20 % after 4 hour s of incubation with either drug (5 % in controls). Apoptosis was conf irmed by DNA fragmentation, and was blocked by calcium chelators and i nhibitors of protein synthesis. The apoptotic effect of microtubule di srupting drugs (MDD) was directed to interphase thymocytes and was ind ependent on MDD action on mitotic cells. However, cell death of mitoti cally arrested cells showed ultrastructural changes similar in many as pects to apoptosis.