DNA excision-repair processes in human cells can eliminate the cytotoxic and mutagenic consequences of ultraviolet irradiation |
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Authors: | V M Maher D J Dorney A L Mendrala B Konze-Thomas J J McCormick |
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Affiliation: | Department of Microbioloby and Department of Biochemistry, Carcinogenesis Laboratory, Fee Hall, Michigan State University, East Lansing, MI 48824 U.S.A. |
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Abstract: | The ability of DNA excision-repair processes in diploid human fibroblasts to eliminate potentially cytotoxic and mutagenic lesions induced by UV radiation (254 nm) was demonstrated in two ways: (1) Cells with normal rates of excision were compared with cells with an intermediate rate of excision (XP2BE) and cells with an excision rate less than or equal to 1% that of normal (XP12BE) for sensitivity to the killing and mutagenic action of UV radiation. The normal cells proved resistant to doses of UV which reduced the survival of the XP cells to 14% and 0.7%, respectively, and increased the frequency of mutations to 8-azaguanine resistance in the XP cells 5- to 10-fold over background. (2) Cells in confluence were irradiated with cytotoxic and mutagenic doses of UV and allowed to carry out excision repair. After various lengths of time they were replated at lower densities to allow for expression of mutations to 6-thioguanine resistance and/or at cloning densities to assay survival. Normal cells and XP cells with reduced rates of excision repair (from complementation groups C and D) exhibited a gradual increase in survival from an initial level of 15--20% to 100% if held approximately 20 h in confluence. In contrast, XP12BE cells showed no increase from an initial survival of 20% even when held for 7 days. Normal cells irradiated in confluence but prevented from replicating for 7 days exhibited background mutation frequencies, whereas the mutation frequency in XP12BE cells did not change with the time in confluence. |
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Keywords: | AG 8-azaguanine azaguanine-resistant CS calf serum CV bulk cell culture vessels FCS fetal calf serum HEPES HPRT hypoxanthine(guanine)phosphoribosyltransferase, EC 2.4.2.8 gene coding for the enzyme, HPRT HX hypoxanthine LN Lesch Nyhan syndrome NF (normal fibroblasts) i.e., diploid fibroblasts derived from normal individuals PBS phosphate-buffered saline pH 7.2 TG 6-thioguanine thioguanine resistant XP xeroderma pigmentosum |
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