DIMETHYL-SULFOXIDE SUPPRESSES APOPTOSIS IN BURKITTS-LYMPHOMA CELLS

Previous reports have suggested that dimethyl sulfoxide (DMSO) may be a useful reversible G(1) arresting agent for synchronizing Raji Burkit t's lymphoma cells (K. Takase et al. (1992) Cell Growth Differ. 3, 515 -521; M. Sawai et al. (1990) Exp. Cell Res. 187, 4-10). We have theref ore critically evaluated several aspects of DMSO's effects using Daudi and Ramos Burkitt's lymphoma (BL) cells. In BL cells starved in the p resence or absence of DMSO for 4 to 6 days (approximately four to six doubling times), the following observations were noted: (A) Both Daudi and Ramos cells show increased cell synchrony accompanied by apoptosi s when starved in RPMI 1640 supplemented with 10% fetal calf serum (FC S). Inclusion of 1.5% DMSO causes a diminution in apoptosis with minim al effects on synchrony. (B) Lowering the FCS concentration to 5% indu ces apoptosis. DMSO-mediated protection from apoptosis is observed in Daudi but not in Ramos. (C) When human serum (10%) is used instead of FCS, Daudi cells show no apoptosis and DMSO is without effect on cell cycle distribution. By contrast, Ramos cells show significant apoptosi s, which is prevented by the inclusion of DMSO. (D) When starved in a chemically defined medium (AIM-V), both Daudi and Ramos cells show sig nificant apoptosis. DMSO protects Ramos from apoptosis under these con ditions. (E) Upon removal of DMSO, both Daudi and Ramos cells reenter the cell cycle but with significant apoptosis. (F) The protective effe ct of DMSO from apoptosis is observed in a narrow range of concentrati on between 1 and 2%. At higher concentration, DMSO itself induces apop tosis. These results suggest that DMSO itself prevents apoptosis, an e ffect which may present as an apparent effect on cell synchrony. (C) 1 995 Academic Press, Inc.