INHIBITION OF PHENOLSULFOTRANSFERASE BY SALICYLIC-ACID - A POSSIBLE MECHANISM BY WHICH ASPIRIN MAY REDUCE CARCINOGENESIS

Background-Recent epidemiological evidence has shown that chronic use of aspirin decreases susceptibility to bowel cancer. Animal studies ha ve shown that sulphotransferase inhibitors coadministered with sulphat ion activated carcinogens dramatically reduce the incidence of cancer. Aims-To investigate the effect of the main aspirin breakdown product, salicylic acid, on the P and M isoforms of phenolsulphotransferase fr om human platelets and colonic mucosa. Methods-Platelets were obtained from healthy blood donors and isolated within 24 hours after donation . Samples of colonic mucosa were obtained at resection for non-maligna nt disease. Phenolsulphotransferase activity was measured in cellular homogenates using a standard radiolabelling assay. Results-Salicylic a cid consistently and selectively inhibited the P form of phenolsulphot ransferase at subtherapeutic concentrations in both tissue samples. A 50% inhibition of sulphation by the P phenolsulphotransferase occurred at salicylic acid concentrations of about 40 and 130 mu M in platelet s and bowel mucosa respectively. M phenolsulphotransferase was virtual ly unaffected by salicylic acid up to a concentration of 1.5 mM (the t herapeutic plasma concentration for salicylates when treating rheumato id arthritis is about 1-2 mM). Conclusion-The action of salicylic acid on P phenolsulphotransferase, by preventing the excessive activation of carcinogens, is a possible additional pathway by which aspirin can reduce cancer risk.