REGULATION OF TRANSFORMING GROWTH FACTOR-BETA-1-MEDIATED APOPTOSIS INHEAD AND NECK SQUAMOUS-CELL CARCINOMA

The apoptotic cell death in Cal-27 cells induced by exposure to transf orming growth factor-beta 1 was inhibited by the endonuclease inhibito r aurintricarboxylic acid (ATA) in a concentration-dependent fashion. In vitro studies of cytotoxicity, DNA fragmentation, and protein synth esis by Cal-27 cell lines were performed, Inhibition of cytotoxicity a s well as endonucleolytic DNA cleavage was detected. ATA did not inhib it cytotoxicity either via transforming growth factor cell-surface-rec eptor alteration or by inhibition of macromolecular synthesis. ATA-sen sitive events occurred late during treatment. These data suggest that endonucleolytic DNA cleavage is a mandatory event leading to cell deat h in this system.