DNA fragmentation and ultrastructural changes in the brain of rabbits treated with vincristine

Numerous anticancer drugs, which are in current use, have been shown to induce apoptosis in susceptible cells of some tissues. The aim of the study was to examine whether vincristine injected parenterally to rabbits may affect DNA and ultrastructure of cells in the brain. Vincristine 0.25 mg/kg of body weight was injected to immature (seven day-old) and adult (90 day-old) rabbits. Two, four and six hours after treatment, the significant increased number of cells with internucleosomal fragmentation of DNA was found. At the same time, in some glial cells characteristic for apoptosis condensation of chromatin was observed. Numerous apoptotic bodies were scattered throughout the tissue or digested by neighboring cells (astroglia, oligodendroglia, microglia and pericytes). The result provided evidence that vincristine treatment may induce apoptosis and trigger phagocytic clearance of apoptotic bodies in the brain. Presumably, both of these processes participate in neurotoxic effect of the drug on the CNS during chemotherapy.