Summary
The ability of DNA excision-repair processes in diploid human fibroblasts to eliminate potentially cytotoxic and mutagenic lesions induced by UV radiation or several chemical carcinogens, including N-acetoxy-2-acetylaminofluorene or the “anti” 7,8-diol-9,10-epoxide of benzo(a)pyrene, was investigated. Cells with normal rates of excision were compared with cells with an intermediate rate of excision (XP2BE or XP5BE) and cells with an excision rate ∼1% that of normal (XP12BE) for sensitivity to the killing and mutagenic action of these agents. The normal cells proved resistant to doses which significantly reduced the survival of the XP cells and increased the frequency of mutations to 8-azaguanine resistance in the XP cells 5- to 10-fold over background. Cells in confluence were exposed to cytotoxic and mutagenic doses of these agents 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 or D) exhibited a gradual increase in survival from an initial level of 15–20% to 80–100% if held in confluence. Recovery from UV irradiation was complete in less than 24 hours, whereas after treatment with the chemical agents, repair continued for several days and recovery followed similar kinetics. In contrast, XP12BE cells showed no excision repair and no increase from an initial survival of 20%, even when held for 7 days. Normal cells treated with these agents in confluence, but prevented from replicating for 7 days, exhibited background or near background mutation frequencies, whereas the mutation freuency in XP12BE cells did not change with the time in confluence.
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© 1980 Plenum Press, New York
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McCormick, J.J., Maher, V.M. (1980). DNA Repair Processes can alter the Frequency of Mutations Induced in Diploid Human Cells. In: Generoso, W.M., Shelby, M.D., de Serres, F.J. (eds) DNA Repair and Mutagenesis in Eukaryotes. Basic Life Sciences, vol 15. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-3842-0_20
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DOI: https://doi.org/10.1007/978-1-4684-3842-0_20
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