P53 INVOLVES CYTOSINE ARABINOSIDE-INDUCED APOPTOSIS IN CULTURED CEREBELLAR GRANULE NEURONS

The tumor suppressor p53 gene plays a key role in controlling the cell cycle checkpoint and in apoptosis following the exposure of normal ce lls to DNA damage. To investigate the role of p53 in cytosine arabinos ide (Ara C)-induced cell death of CNS neurons, we examined the effect of Ara C on the survival of cultured cerebellar granule neurons from n ormal wild-type and p53 null mutant mice, When the neurons from wild-t ype mice were cultured with Ara C, they gradually died after 24 h in c ulture. In contrast, the neurons from p53 null mutant mice showed a re sistance to the Ara C neurotoxicity. These results indicate that p53 i nvolves Ara C-induced apoptosis in cultured cerebellar granule neurons , in which DNA damage may initiate the apoptotic death program of the neurons.