32P-postlabelling studies of target tissues and bile from patients with familial adenomatous polyposis and from...

Patients with the inherited form of colon cancer, familial adenomatous polyposis (FAP), are at high risk of developing duodenal adenomas and carcinomas. The periampullary clustering of these neoplasms suggests that bile plays a role in their development. We investigated this theory using 32P-postlabelling to detect DNA adducts. We found significantly higher adduct levels in duodenum of FAP patients than in unaffected controls, and higher levels in duodenum than stomach. Levels of adducts were significantly higher in the small bowel of rats gavaged with FAP gallbladder bile than in the small bowel of those that received control gallbladder bile. We found that bile from FAP gallbladder produced significantly more DNA adducts than control gallbladder bile when incubated with salmon sperm DNA in vitro. These results support the hypothesis that the bile of FAP patients may be involved in the development of duodenal adenomas in these patients.