ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE BY THE CARCINOGENIC MYCOTOXIN FUMONISIN B-1

Recent studies indicate that the mycotoxin and putative carcinogen fum onisin B-1 stimulates mitogenesis in Swiss 3T3 fibroblasts. Because mi togen-activated protein kinase (MAPK) is a key enzyme in the signal tr ansduction pathways activated by many mitogens, we hypothesized that f umonisin B-1 might modulate MAPK activity. Consistent with other repor ts, we observed that fumonisin B-1 is synergistic with insulin for mit ogenesis in Swiss 3T3 cells. We also observed that: (1) fumonisin B-1 stimulates rapid, transient activation of MAPK; and (2) the dose-respo nse curve for fumonisin B-1-stimulated activation of MAPK is similar t o the dose-response curve for the mitogenic effects of fumonisin B-1. In contrast to fumonisin B-1, insulin stimulates minimal activation of MAPK in Swiss 3T3 cells. The observation that fumonisin B-1 and insul in differ with respect to the modulation of MAPK activity suggests a p ossible mechanism for their synergistic stimulation of mitogenesis in Swiss 3T3 cells. (C) 1996 Academic Press, Inc.