RADIATION-INDUCED APOPTOSIS IN F9 TERATOCARCINOMA CELLS

We have found that F9 murine teratocarcinoma cells undergo morphologic al changes and internucleosomal DNA fragmentation characteristic of ap optosis after exposure to ionizing radiation. We studied the time cour se, radiation dose-response, and the effects of protein and RNA synthe sis inhibitors on this process. The response is dose dependent in the range 2-12 Gy. Internucleosomal DNA fragmentation can be detected as e arly as 6 h postirradiation and is maximal by 48 h. Cycloheximide, a p rotein synthesis inhibitor, and 5,6-dichloro-1-beta-D-ribofuranosylben zimidazole, an RNA synthesis inhibitor, both induced internucleosomal DNA fragmentation in the unirradiated cells and enhanced radiation-ind uced DNA fragmentation. F9 cells can be induced to differentiate into cells resembling endoderm with retinoic acid. After irradiation, diffe rentiated F9 cells exhibit less DNA fragmentation than stem cells. Thi s indicates that ionizing radiation can induce apoptosis in non-lympho id rumours. We suggest that embryonic tumour cells may be particularly susceptible to agents that induce apoptosis.