We have compared responses of cells from two genetic disorders, Cockayne's syndrome (CS) and xeroderma pigmentosum complementation group C (XP-C), both of which exhibit cellular hypersensitivity to sunlight, but only one of which, XP, manifests a high rate of sunlight-induced cancer. CS cells, in contrast to XP cells, showed a normal G2 response to irradiation with either x-rays or near-UV visible light. However, CS cells showed a deficiency in repair of DNA damage inflicted by light during S and G1 phases of the cell cycle. The present results support the concept that deficient DNA repair during G2 phase plays a role in carcinogenesis. Addition of the DNA repair inhibitor, caffeine, after G1 light exposure had little effect on chromatid breaks or gaps in normal cells but significantly increased frequencies of chromatid breaks in CS cells and both breaks and gaps in XP cells. The results suggest that CS and XP noncycling cells, such as neurons, may accumulate damage that in cycling skin fibroblasts would be repaired during S and G2 phases . Thus, the repair deficiencies in CS and XP may account for the neurologic degeneration associated with these two genetic diseases. A deficiency in DNA repair, manifest as persistent chromatid damage after G2 phase x- irradiation, was acquired spontaneously or induced by ras oncogene in continuous lines of human mammary epithelial cells in culture prior to or in association with their malignant neoplastic transformation. As reported previously for human epidermal keratinocytes (Cancer Res 1987;47:1390), acquisition of the repair-deficient phenotype appears to be an early requisite step in the malignant neoplastic transformation of human cells in culture.
