ENHANCED APOPTOSIS IN TRANSFORMED HUMAN LUNG FIBROBLASTS AFTER EXPOSURE TO SODIUM-BUTYRATE

Simian virus-transformed human cells, WI-38 VA13A, showed a dose-depen dent induction of apoptosis and reduction in cell numbers after exposu re to sodium butyrate. Apoptosis was confirmed by ApopTag staining, is olation of apoptotic envelopes, and immunofluorescent staining with an antibody specific for apoptotic envelopes. Examination of the cell cu ltures by phase contrast and fluorescent microscopy revealed the prese nce of enlarged cells that displayed a more flattened morphology and m orphological changes in the nucleus of cells exposed to sodium butyrat e. Cell proliferation assays showed control and sodium butyrate cultur es were synthesizing DNA and excluded any cytotoxic effects of sodium butyrate. Flow cytometry results indicated an increase in the number o f aneuploid cells following sodium butyrate treatment. There was a dec rease in the percentage of cells in G2/M in the diploid populations, b ut an increase in the percentage of cells in G2/M in aneuploid populat ions. This human in vitro model system suggests a mode of action for t he therapeutic effects of sodium butyrate, which have been observed in the topical treatment of neoplastic cells and reversal of symptoms in ulcerative colitis: namely, the induction of apoptosis.