Abstract
RESISTANCE to the cytotoxic purine analogue 6-thioguanine (TG) in cultured mammalian cells is known to be associated with deficiency in the X-chromosome-linked purine-salvage enzyme, hypoxanthine-guanine phosphoribosyl transferase (HGPRT, EC 2.4.2.8). The induction of mutations to TG resistance in cultured mammalian cells has been used to quantify the mutagenic effects of various physical and chemical agents1–3 and it has been argued that such mutations arise primarily as a result of true gene mutations4. However, because ionising radiation induces TG-resistant mutants with very low HGPRT activity5 and fails to induce the ouabain-resistance phenotype in mammalian cells6,7, it has been suggested that ionising radiation leads to gross genetic damage rather than to point mutations in structural genes2,7. Here we present evidence that gross structural changes involving the X chromosome are the genetic basis of a significant proportion of radiation-induced mutation to TG resistance in cultured human fibroblasts.
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COX, R., MASSON, W. Do radiation-induced thioguanine-resistant mutants of cultured mammalian cells arise by HGPRT gene mutation or X-chromosome rearrangement?. Nature 276, 629–630 (1978). https://doi.org/10.1038/276629a0
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DOI: https://doi.org/10.1038/276629a0
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