The chemopreventive role of ursodeoxycholic acid in azoxymethane-treated rats: suppressive effects on enhanced group II phospholipase A(2) expressionin colonic tissue

Great interest has been focused on the chemoprevention of colonic carcinoge nesis by oral administration of ursodeoxycholic acid (UDCA) because its adm inistration reportedly reduces the incidence of colon cancer in animal expe riments. To elucidate the precise role of UDCA in the chemoprevention of az oxymethane-induced colon carcinogenesis, we examined the expression levels of group II phospholipase A(2) in the colonic tissue of UDCA-treated and un treated rats and correlated the levels with the findings of aberrant crypt foci, putative preneoplastic lesions. Twelve weeks after azoxymethane expos ure, the total number of aberrant crypt foci in 0.4% UDCA-fed rats and 1% U DCA-fed rats was significantly decreased compared to the untreated animals. The mucosal concentrations of PGE(2) and 6-keto PGF1 alpha were significan tly lower in the UDCA-treated rats than in untreated rats. In correlation w ith lowering, the enhanced activity, protein mass and mRNA levels of group II phospholipase A(2) were significantly attenuated in the UDCA-treated ani mals. The chemopreventive role of UDCA in colon carcinogenesis may lie in i ts modulation of the arachidonate metabolism in colonic mucosa. (C) 1998 El sevier Science Inland Ltd. All rights reserved.