INHIBITION OF DNA-SYNTHESIS BY ASPIRIN IN SWISS 3T3 FIBROBLASTS

In Swiss 3T3 fibroblasts, aspirin inhibited proliferation induced by t he complete mitogenic factors platelet-derived growth factor (PDGF) an d bombesin, Aspirin decreased the maximum mitogenic effect of bombesin without modifying the concentration necessary to obtain half maximal DNA synthesis stimulation, in contrast, aspirin only decreased mitogen esis at subsaturating PDGF concentrations. The effect of aspirin was f ound to be concentration dependent, The half-maximal effect occurred a t approximately 150 mu M. The maximal inhibition was obtained when asp irin was added during the first hour after growth factor addition. At this time, both PDGF and bombesin induced prostaglandin E(2) synthesis . PDGF induced much higher levels of prostaglandin E(2) than bombesin. The inhibitory effects of aspirin an PDGF or bombesin-stimulated DNA synthesis were counteracted by 280 nM prostaglandin E(2), Aspirin effe cts were overcome by agents that increase cellular cyclic adenosine mo nophosphate levels but not by activation of protein kinase C. The sign ificance of the antiproliferative action of aspirin might be associate d with epidemiological data that show a reduced incidence of colorecta l and other cancers after aspirin treatment.