APOPTOSIS IS INDUCED AT NONPERMISSIVE TEMPERATURE BY A TRANSIENT INCREASE IN P53 IN CELL-LINES IMMORTALIZED WITH TEMPERATURE-SENSITIVE SV40 LARGE T-ANTIGEN GENE

Hepatocyte (TLRB) and kidney tubule (TKC2) cell lines established from temperature-sensitive (ts) SV40 T-antigen gene transgenic mice not only were arrested in growth, but also exhibited cell death at nonpermissive temperature (39 degrees C). The cell death was determined to be caused by apoptosis from observations of nuclear fragmentation and DNA fragmentation. These cell lines contained relatively high levels of wild-type p53 which formed complexes with T-antigen at permissive temperature (33 degrees C), but after shift to a nonpermissive temperature, the inactivation of T-antigens led to the liberation of an abundance of p53 proteins from the complexes, apparently inducing apoptosis. (C) 1994 Academic Press, Inc.