Glutamate and antimitotic agents induce differentiation, p53 activation, and apoptosis in rodent neostriatal cell lines immortalized with the tsA58 allele of SV40 large T antigen

The tsA58 allele of SV40 large T antigen has the ability to immortalize cel ls, which is thought to be due, in part, to binding of p53 protein by T ant igen at 33 degrees C. At the nonpermissive temperature (39.5 degrees C), it is thought that p53 is released, inducing growth arrest, vulnerability to apoptosis, and loss of the immortal phenotype. In cell lines derived from t he rat neostriatum immortalized with tsA58, the toxic agents Adriamycin, cy tosine arabinoside, and glutamate induced apoptosis and increased p53 activ ity and differentiation. The apoptosis and p53-inducing effects of the drug s were not greater at 39.5 degrees C compared to 33 degrees C, suggesting t hat p53 is not effectively blocked even at 33 degrees C. Growth arrest was not induced under most treatment conditions despite p53 induction. On the o ther hand, process extension was enhanced at 39.5 degrees C compared to 33 degrees C. Therefore, these cell lines are temperature sensitive with respe ct to differentiation, but not growth regulation or apoptosis. (C) 1999 Aca demic Press.