Deficient DNA repair in chronic ulcerative colitis

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 chromatid 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.