THE DIFFERENT INHIBITING EFFECT OF CHOLERA-TOXIN ON 2 LEUKEMIA-CELL LINES DOES NOT CORRELATE WITH THEIR TOXIN BINDING-CAPACITY

The murine leukemia cell lines L1210 and WEHI-3B show a very different sensitivity to the cholera toxin (CT). The in vitro growth of L1210 i s completely inhibited by 10(-8) M CT, while WEHI-3B growth shows the same inhibition at 10(-11) M. The analysis of membrane ganglioside pat tern of the two cell lines shows that in L1210 cells the major compone nt is the GM1a ganglioside while the monosialoganglioside fraction fro m WEHI-3B is entirely composed of gangliosides of the 'b' series among which GM1b is the more represented. The total cholera toxin binding c apacity of the ganglioside extract from L1210 cells is more than hundr ed fold higher than that of WEHI-3B and this difference is also confir med by the number of CT receptors/cell and by the binding of FITC-B su bunit of CT on the cells. These surprising data are in conflict with t he poor sensitivity to CT evidenced by L1210 compared to WEHI-3B cells . In order to clarify this discrepancy we investigated the cAMP accumu lation, the cell viability and the clonogenicity of these two leukemia cell lines following the treatment with CT and forskolin (FRSK). The treatment of WEHI-3B cells with CT induces a dramatic increase of intr acellular cAMP which highly correlates with cell death and the decreas e of clonogenicity and this result is partially obtained by the treatm ent with FRSK. L1210 cells do not evidence significant cAMP accumulati on neither with CT nor with FRSK treatment. These data suggest that th e different inhibiting effect of CT on WEHI-3B and L1210 cells does no t correlate with their different pattern of gangliosides and the relat ed toxin binding capacity. Further they indicate that the growth inhib ition of WEHI-3B cells is closely related with a cAMP-dependent cell k illing mechanism, while the inhibition of L1210 growth (produced by hi gh concentration of CT) is mediated by a cAMP independent mechanism.