Chromatid damage after G2 phase x-irradiation of cells from cancer-prone individuals implicates deficiency in DNA repair.

Ten lines of skin fibroblasts from individuals with genetic disorders predisposing to a high risk of cancer were compared with nine lines from normal adult donors with respect to chromatid damage after x-irradiation [25, 50, and 100 rad (0.25, 0.50, and 1 gray)] during G2 phase. The 10 cell lines represented five genetic disorders: Bloom syndrome, familial polyposis, Fanconi anemia, Gardner syndrome, and xeroderma pigmentosum, complementation groups A(XP-A), C(XP-C), E(XP-E), and variant (XP-Va). The incidence of chromatid breaks in all cancer-prone lines except XP-E and XP-A was significantly higher than in the normal lines. The incidence of chromatid gaps in all cancer-prone lines except XP-A and XP-Va was significantly higher than in the normal lines. Because each chromatid apparently contains a single continuous DNA double strand, chromatid breaks and gaps represent unrepaired DNA strand breaks arising directly or indirectly during excision repair of x-ray-induced DNA damage. These cytogenetic data together with results from use of the DNA repair inhibitor arabinofuranosyl cytosine (cytosine arabinoside) suggest that cells from all of these cancer-prone individuals are deficient in some step of DNA repair, predominantly excision repair operative during the G2-prophase period of the cell cycle. It appears that these DNA repair deficiencies are associated with a genetic predisposition to a high risk of cancer.