Phytohemagglutinin rapidly lyses S49 T-lymphoma cells and the cytotoxicity is not mediated by generation of cAMP or increase in cytosolic calcium

Thymic-like lymphomas are very sensitive to killing by phytohemagglutinin. To investigate the mechanism of cytotoxicity, we studied the effect of PHA on cytosolic calcium ( Ca2+]i) and cAMP in the S49 mouse lymphoma cell line. PHA produced a slow continuing rise in Ca2+]i. Estimation of cell number by Coulter counting showed that PHA induced rapid lysis of S49 cells in a dose-dependent manner. Nicardipine (10(-5) M) did not prevent PHA induced cell lysis or Ca2+]i increase. Also ionomycin (10(-7) M) did not induce cell lysis. The data suggest that PHA induced increase in Ca2+]i is the result rather than the cause of cell lysis. Elevated intracellular cAMP has an antiproliferative effect on S49 cells. PHA had no effect on cAMP levels in S49 cells. Also S49 cyc- clone which is deficient in Gs was susceptible to killing by PHA. These results suggest that the cytotoxic effect of PHA on S49 cells is rapid, but is not mediated by cAMP generation or an increase in Ca2+]i, and other mechanisms should be investigated.