MODULATION OF FIBROBLAST RESPONSE TO MAITOTOXIN ALONG THE CELL-DIVISION CYCLE

Maitotoxin (MTX) induces an increase of [Ca2+](i), and of phosphoinosi tide breakdown in various cell types. The [Ca2+](i) increase followed with fluorescent probes on cell suspensions has been described as slow and lasting, in contrast to the ''signal'' induced by calcium ionopho res such as ionomycin. MTX effects have been studied on two fibroblast ic cell lines, BHK21 C13 and FR 3T3, synchronized by serum deprivation treatment performed in an isoleucine-free medium for BHK21 C13 cells. In BHK21 C13 cells, flow cytometry analysis showed that two stages, G 1/S and G2/M, were particularly susceptible to MTX treatment. Scanning laser cytometry demonstrated that calcium response of FR 3T3 fibrobla sts followed with Indo-1 varied during the cell division cycle. The [C a2+](i) increase was almost always vertical, but its delay after MTX a ddition lasted from zero (S and G2/M transition) to 10-20 min (G1) or more (G2). No [Ca-?(2+)](i) change could be detected during mitosis. T he [Ca2+](i) response at the S phase was biphasic. These observations suggest that (1) the lasting response described in the literature repr esents a global cell population effect, and (2) cells are more sensiti ve to MTX at specific stages of the cell division cycle, which could c orrespond to periods when calcium signals have been detected in differ ent cell types.