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Various Levels of DNA Repair Synthesis in Xeroderma Pigmentosum Cells exposed to the Carcinogens N-Hydroxy and N-Acetoxy-2-acetyl-aminofluorene

Abstract

IN assessing environmental health hazards, the question has arisen of whether “safe”, “tolerable” or “permissible” levels of carcinogens, mutagens or teratogens can be derived by extrapolation of bioassays using rodents exposed for various periods to very high concentrations of chemicals or using cultured mammalian cell lines. Variations in susceptibility are only rarely taken into account, if at all, and doses which seem to be harmless to the average person may be harmful to susceptible people. The reduced capacity to repair ultraviolet-induced DNA lesions in xeroderma pigmentosum (XP) cells may exemplify a mechanism leading to an elevated neoplastic transformation rate in man1–4. The question arises as to whether cells with deficient repair synthesis respond to chemical carcinogens in the same manner as cells with adequate repair systems. We report here the levels of DNA repair synthesis in XP cells of five patients exposed to the carcinogenic5,6 and mutagenic7 compounds N-acetoxy or N-hydroxy-2-acetyl-aminofluorene, which are ultimate and proximate carcinogenic forms of 2-acetylaminofluorene (AAF). We were particularly interested in comparing the different levels of DNA repair synthesis following ultraviolet irradiation with those following treatment with chemical carcinogens.

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STICH, H., SAN, R., MILLER, J. et al. Various Levels of DNA Repair Synthesis in Xeroderma Pigmentosum Cells exposed to the Carcinogens N-Hydroxy and N-Acetoxy-2-acetyl-aminofluorene. Nature New Biology 238, 9–10 (1972). https://doi.org/10.1038/newbio238009a0

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