Abstract
XERODERMA pigmentosum (XP) is an inherited human disease clinically characterised by abnormal pigmentation patterns and the development of multiple skin carcinoma on areas exposed to the Sun1. Cells from most XP patients are defective in excision repair of ultraviolet-induced lesions in DNA1–3, but there is a class of patients—XP variants—who have all the clinical manifestations of the disease but who, until recently, appeared to have normal DNA repair. Cleaver4 and others5,6 have shown that variants have normal rates of excision repair of damage caused by ultraviolet light as measured by ultraviolet-stimulated uptake of labelled thymidine or bromodeoxyuridine. Cleaver also reported that variants XP4BE (his patient 13) and XP13BE (his patient 14) have normal sensitivity to ultraviolet light as measured by survival of colony-forming ability4. His survival data, however, consisted of only two points for each strain. As Fig. 1 shows, we find that the percentage survival of the colony-forming ability of variants XP4BE and XP13BE as well as variant XP7TA and XP30RO is more sensitive to ultraviolet irradiation than that of normal cells. We also showed that the survival of the cloning ability of XP variants is more sensitive than normal to active derivatives of four aromatic amide carcinogens7 and to the K-region epoxides of three polycyclic hydrocarbons8. These two classes of carcinogens bind covalently to DNA9,10 and the bound adducts seem to be recognised by the same repair enzymes which function in the repair of ultraviolet-induced damage in these human cells7–11.
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MAHER, V., OUELLETTE, L., MITTLESTAT, M. et al. Synergistic effect of caffeine on the cytotoxicity of ultraviolet irradiation and of hydrocarbon epoxides in strains of Xeroderma pigmentosum. Nature 258, 760–763 (1975). https://doi.org/10.1038/258760a0
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DOI: https://doi.org/10.1038/258760a0
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