The role of apoptosis in growing and stationary rat ascites hepatoma, Yoshida AH-130.

The occurrence of apoptosis and its contribution to growth-phase transitions in the rat ascites hepatoma Yoshida AH-130 have been evaluated. Apoptosis was observed by light microscopy in both exponentially-growing and stationary tumours as characteristic chromatin condensation and compacting of the cytoplasm, but the frequency of apoptotic bodies (apoptotic index) was four-fold higher in stationary than in logarithmic-growing tumours. Apoptosing cells exhibited strong immunocytochemical reactivity for 'tissue' transglutaminase, and transglutaminase activity was higher in stationary tumour cells. A ladder pattern of DNA fragmentation was revealed by agarose gel electrophoresis which was more pronounced in stationary tumours. The apoptotic bodies were either free or contained in vacuoles within otherwise normal tumour cells, suggesting active engulfment of dead cells by viable homologous cells. Such 'homophagic' disposal of the apoptotic bodies probably accounted for a component of the enhanced cell protein degradation previously observed in stationary AH-130 tumours (Tessitore L, Bonelli G, Cecchini G, Amenta JS, Baccino FM, Arch Biochem Biophys 1987; 255: 372-384). The data indicate that, in concurrence with changes in the cell proliferation rate, modulations of apoptosis play a substantial role in determining the net growth rate of such an anaplastic tumour as the Yoshida AH-130 hepatoma.