Abstract
We are investigating the mechanisms by which mutations are introduced into the DNA of diploid human fibroblasts following exposure to chemical carcinogens or ultraviolet (UV) radiation. In particular, we have asked, are the mutations induced by these agents introduced during the repair process by misrepair? or are they the result of misreplication during semi-conservative DNA synthesis? Our studies have been facilitated by the existence of excision repair-proficient diploid human cells derived from normal persons and repair-deficient fibroblasts derived from xeroderma pigmentosum (XP) patients. We have compared these fibroblasts for their response to the mutagenic and/or cytotoxic effect of UV radiation, 1–5 of reactive derivatives of a series of aromatic amines6,7 or polycyclic aromatic hydrocarbons,8–11 hr of nitrosoureas. 12 Cytotoxicity is defined as the inability of a cell to form a colony, i.e., reproductive death. Mutagenicity is defined as an increase in 8-azaguanine or 6-thioguanine resistant cells in the population (resulting from the loss of active hypoxanthine(guanine)phosphorylbosyltransferase). The results of our studies indicate that mutations by these particular agents are not introduced during excision repair but result directly or indirectly from semi-conservative DNA synthesis on a template containing unexcised lesions, i.e., by misreplication or failure to replicate a portion of the DNA.
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References
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© 1983 Plenum Press, New York
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Maher, V.M., McCormick, J.J. (1983). Relationship Between Excision Repair and the Cytotoxic and Mutagenic Action of Chemicals and UV Radiation. In: Lawrence, C.W. (eds) Induced Mutagenesis. Basic Life Sciences, vol 15. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4382-0_11
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DOI: https://doi.org/10.1007/978-1-4684-4382-0_11
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