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 cells, which is thought to be due, in part, to binding of p53 protein by T antigen 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 the rat neostriatum immortalized with tsA58, the toxic agents Adriamycin, cytosine arabinoside, and glutamate induced apoptosis and increased p53 activity and differentiation. The apoptosis and p53-inducing effects of the drugs were not greater at 39.5 degrees C compared to 33 degrees C, suggesting that p53 is not effectively blocked even at 33 degrees C. Growth arrest was not induced under most treatment conditions despite p53 induction. On the other hand, process extension was enhanced at 39.5 degrees C compared to 33 degrees C. Therefore, these cell lines are temperature sensitive with respect to differentiation, but not growth regulation or apoptosis.
Conejero
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C
National Institute on Drug Abuse, Cellular Neurobiology Branch, Baltimore, Maryland 21224, USA.
Wright
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Freed
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D000483:Alleles; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects* / Q000648:ultrastructure*; D009447:Neuroblastoma / Q000648:ultrastructure; D051381:Rats; D019572:Retinal Neoplasms / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects*
D000952:Antigens, Polyomavirus Transforming; D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D003561:Cytarabine; D018698:Glutamic Acid; D004317:Doxorubicin