Published in Cancer Detection and Prevention 1997; 21(6):540-545.

Deficient DNA Repair in Chronic Ulcerative Colitis

Katherine K Sanford PhDa, Floyd M Price MSa, Carmel Brodeur BS RNb, Frederick L Makrauer MDb, Ram Parshad PhDc

aLaboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD; bGastroenterology, Wellesley Hills Medical Center, Wellesley, MA; cDepartment of Pathology, Howard University College of Medicine, Washington, DC

Address all correspondence and reprint requests to: Katherine K. Sanford, Ph.D., Room 1E24, Bldg. 37, National Institutes of Health, Bethesda, MD 20892.

ABSTRACT: Carcinoma of the colon is a serious complication of chronic ulcerative colitis (CUC), a disease of unknown etiology. Peripheral blood lymphocytes from nine patients with CUC showed deficient repair of radiation-induced DNA damage compared with a group of healthy controls. DNA repair was measured indirectly by quantifying chromatid breaks after irradiation of cells with X-rays or ultraviolet during G2 phase of the cell cycle. Such breaks represent unrepaired DNA strand breaks that may arise directly from the damaging agent or indirectly during repair processes. Two types of deficiency were revealed. One was an abnormally high frequency of chromatic breaks after G2-phase X-irradiation. These may reflect deficient strand-break repair. The second deficiency was manifest as a low frequency of breaks not increased by addition of the DNA repair inhibitor araC. This low frequency apparently results from negligible incision activity. Deficient DNA repair in CUC may thus be a requisite predisposing factor for genomic instability and the potential development of colon carcinoma.

KEY WORDS: chromatid breaks, G2 phase, ultraviolet irradiation, X-irradiation.