DNA fragmentation in S49 lymphoma cells killed with glucocorticoids and other agents.

The effects of glucocorticoids on DNA integrity in the mouse S49 lymphoma cell line were assessed. DNA cleavage at the internucleosomal regions was observed, and this response was correlated to the dose of hormone used and the time of treatment. Also, an apparent steroid specificity was observed: internucleosomal cleavage was associated only with treatment of the cells with glucocorticoids. Cells treated with dibutyryl cyclic AMP (which also causes lymphocytolysis) also exhibited DNA cleavage. However, when cells were killed with various DNA synthesis inhibitors and other lethal agents, the same DNA cleavage pattern was observed. Furthermore, new protein synthesis did not seem to be required, since cells killed with puromycin and cycloheximide also exhibited internucleosomal DNA fragmentation. Although DNA fragmentation may not be a specific early effect of glucocorticoid-mediated lymphocytolysis, it may be the final, irrevocable step in this complex process.