HIGH PH REDUCES DNA-DAMAGE CAUSED BY BILE FROM PATIENTS WITH FAMILIALADENOMATOUS POLYPOSIS - ANTACIDS MAY ATTENUATE DUODENAL POLYPOSIS

Patients with familial adenomatous polyposis (FAP) develop periampulla ry duodenal tumours, suggesting that bile contributes to their formati on. The hypothesis that bile contains carcinogens has been tested by l ooking for DNA adducts (markers of carcinogen exposure) in the duodenu m of patients with or without FAP and by determining whether bile can produce DNA adducts in vitro. Using P-32-postlabelling to detect adduc ts, there was an excess (compared with unaffected patients) of DNA add ucts in the duodenum of FAP patients and an excess of DNA adducts in t he small bowel of rats treated with FAP bile, while bile from FAP pati ents formed significantly more DNA adducts in vitro than did bile from controls. In this study it is shown that the excess of adduct labelli ng produced by FAP bile in vitro depends on the pH of the incubate. Wh ile adduct labelling at pH 6-8 did not differ significantly between bi le from six FAP patients and six controls, at pH 4-5 FAP bile, but not control bile, produced a near threefold excess of adduct labelling ov er that at pH 6-8. Therapy that increases duodenal pH may therefore al leviate duodenal polyposis.