The mononuclear leukocytes from peripheral blood samples of individuals with (n = 30) and without (n = 48) colonic polyps were examined for their abilities to carry out unscheduled DNA synthesis (UDS) induced by N-acetoxy-N-2-fluorenylacetamide (N-AcO-2-FAA). Individuals with polyps had significantly reduced UDS values compared to the nonpolyp group (P < 0.01). Furthermore, in a more comprehensive study, patients with hyperplastic polyps had N-AcO-2-FAA-induced UDS values not significantly different from control individuals who were asymptomatic and free from colonic disease as judged by complete colonoscopy. However, patients who had had adenomatous polyps in their large bowel had significantly reduced levels of N-AcO-2-FAA-induced UDS in their mononuclear leukocytes (P < 0.005). When N-AcO-2-FAA binding to DNA determinations were made in parallel and DNA repair proficiency indices were calculated (i.e., N-AcO-2-FAA-induced UDS/N-AcO-2-FAA binding to DNA), the patients with adenomatous polyps were still shown to be deficient in carrying out DNA repair synthesis. Since adenomatous polyps of the large bowel are considered the premalignant lesion for colorectal cancer, we postulate that reduced UDS may be a genetically sensitive marker that is useful in studying the mechanisms of genetic predisposition to colorectal cancer.
Supported by grants from the Elsa U. Pardee Foundation, the Bodman Foundation, and the Swedish Council for Planning and Coordination of Research in “Chemical Health Risks in Our Environment.” Research procedures were in accord with the ethical standard of the Committee on Clinical Investigation of the Strang Clinic and Memorial Sloan-Kettering Cancer Center.