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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Thacker, J. & Cox, R. Nature 258, 429–431 (1975).
Cox, R., Thacker, J., Goodhead, D. T. & Munson, R. J. Nature 267, 425–427 (1977).
O'Neill, J. P. & Hsie, A. W. Nature 269, 815–817 (1977).
Siminovitch, L. Cell 7, 1–11 (1976).
Thacker, J., Stephens, M. A. & Stretch, A. Mutat. Res. 35, 465–478 (1976).
Arlett, C. F., Turnbull, D., Harcourt, S. A., Lehmann, A. R. & Colella, C. M. Mutat. Res. 33, 361–278 (1975).
Thacker, J., Stephens, M. A. & Stretch, A. Mutat. Res. 51, 255–270 (1978).
Brown, J. A. et al. Cytogenet. Cell Genet. 16, 54–59 (1976).
Savage, J. R. K. Nature 270, 513–514 (1977).
Wajntal, A. & De Mars, R. Biochem. Genet. 1, 61–64 (1967).
Savage, J. R. K. J. med. Genet. 14, 362–370 (1977).
Reiger, R., Michaelis, A. & Green, M. H. A Glossary of Genetics and Cytogenetics, Classical and Molecular (Springer, New York, 1968).
Searle, A. G. Adv. Radiat. Biol. 4, 131–207 (1974).
Birth Defects: Original Article Series, Vol. 8, No. 7 (The National Foundation–March of Dimes, New York, 1972).
Cox, R. & Masson, W. K. Mutat. Res. 36, 93–104 (1976).
Summer, A. T., Evans, H. J. & Buckland, R. A. Nature new Biol. 232, 31–32 (1971).
Grzeschnik, K. H., Kim, M. A. & Johannsman, R. Humangenetik 29, 44–59 (1975).
Der Kaloustian, V. M., Byrne, R., Young, W. J. & Childs, B. Biochem. Genet. 3, 299–302 (1969).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/276629a0
- Springer Nature Limited
This article is cited by
-
Characterization of spontaneous and induced mutations in SV40-transformed normal and ataxia telangiectasia cell lines
Somatic Cell and Molecular Genetics (1994)
-
A comparison of the CHO/HGPRT+ and the L5178Y/TK+/? mutation assays using suspension treatment and soft agar cloning: Results for 10 chemicals
Cell Biology and Toxicology (1993)
-
Neue Ergebnisse zur Linearit�t der Dosis/Wirkung-Beziehung strahleninduzierter Mutationen
Naturwissenschaften (1988)
-
Effect of gamma rays at the dihydrofolate reductase locus: Deletions and inversions
Somatic Cell and Molecular Genetics (1986)