Apoptosis Induced by Microtubule Disrupting Drugs in Normal Murine Thymocytes In Vitro

Disruption of cytoplasmic and spindle microtubules by colchicine or nocodazole increases mitotic index, but it also enhances apoptosis in isolated mouse thymocytes; the apoptotic index exceeds 20% after 4 hours of incubation with either drug (5% in controls). Apoptosis was confirmed by DNA fragmentation, and was blocked by calcium chelators and inhibitors of protein synthesis. The apoptotic effect of microtubule disrupting drugs (MOD) was directed to interphase thymocytes and was independent on MOD action on mitotic cells. However, cell death of mitotically arrested cells showed ultrastructural changes similar in many aspects to apoptosis.