Cell killing studies on the mode of action of methotrexate on L-cells in vitro.
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Biomedical subjects
Publications and source records attributed to G F Whitmore.
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Short exposures of mammalian cells to tritiated thymidine of high specific activity destroys the proliferative capacity of mammalian cells. Since the killing is limited to cells that have synthesized DNA in the presence of the labeled compound, an exposure duration of less than one generation can yield a synchronized population.
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Although it has long been evident that the response of eukaryotes to DNA damaging agents is determined by the effectiveness of a variety of DNA repair systems, there is little detailed knowledge of the nature of these systems or the genes which control them. In humans, a number of hereditary conditions, including xeroderma pigmentosum, ataxia telangiectasia and Fanconi's anaemia, exhibit increased sensitivity to a variety of DNA damaging agents and a predisposition to cancer, suggesting a defect in some aspect of DNA repair. This report describes the identification of a human DNA repair gene following DNA-mediated gene transfer into Chinese hamster ovary (CHO) mutant cells, that like xeroderma pigmentosum cells, are sensitive to a variety of DNA damaging agents and are defective in the initial incision step of DNA repair. The resulting transformants exhibit normal resistance to DNA damaging agents and independent transformants demonstrate a common set of human DNA sequences associated with a human DNA repair gene. These observations provide the basis for the isolation and characterization of the human genes responsible for DNA repair.