Defective repair of ultraviolet- and γ-ray damaged DNA in Fanconi's anaemia

Fanconi's anaemia (FA) is one of a group of autosomal recessive syndromes in man. Among other abnormalities, a deficiency in the ability of FA fibroblasts to excise γ-ray induced products of the 5,6-dihydroxydihydrothymine type (t') has been reported (Remsen, J.F., and Cerutti, P.A., Proc. Natn. Acad. Sci., U.S.A., 73:2419 (1976)). This deficiency was not detected in all the FA lines tested. One possibility is that deficiencies in t' excision could be detected in all FA lines if sufficient γ-ray induced damage is present in the DNA. One of the FA lines found to be deficient was also found to be deficient in the excision of UV damage at relatively high doses (Poon, P.K., O'Brien, R.L., and Parker, J.W., Nature, Lond., 250:223 (1974)). A sensitive host-cell reactivation technique has now been used to detect a deficiency in the repair of DNA damaged by either UV or γ-rays in fibroblasts from one of the FA lines reported to have normal t' excision at the levels of γ-ray induced damage employed. Measurements were made of viral structural antigen production 48 hours after infection of fibroblasts by irradiated adenovirus type 2. The method is sensitive, and has the advantage of a reduced assay period. (U.K.)