Mechanisms of Suppression of X-ray-induced Transformation of 10T1/2 Cells by Lipopolysaccharide

Abstract

X-ray induced neoplastic transformation of C3H/10T1/2 cells was suppressed equally by Lipid A and LPS. We examined the effects of several modifiers of arachidonic acid (AA) metabolism in our investigation on the suppression mechanism of LPS. Dexamethasone (DM), an inhibitor of phospholipase A₂ (PLA₂), abolished the effect of LPS, whereas bromophenacyl bromide (BPB), another inhibitor of PLA₂ did not. AA and aspirin neither changed the transformation frequency nor blocked the effect of LPS. TPA, 12-O-tetradecanoyl-phorbol-13-acetate, slightly enhanced radiation transformation, which was diminished by LPS. We also examined the effects of these modifiers on the release of radioactivity from ³H-AA-labeled 10T1/2 cells. No definite correlation was found between the change of AA metabolism and suppression of the transformation frequency by LPS. LPS, however, enhanced dose-dependent myristoylation of the 22 and 67 kDa proteins of 1OT1/2 cells.