Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1974 Dec;71(12):5027–5031. doi: 10.1073/pnas.71.12.5027

Chromosomal Variation and the Origin of Drug-Resistant Mutants in Mammalian Cell Lines

Mario Terzi 1,*
PMCID: PMC434033  PMID: 4531035

Abstract

Drug-resistant mutants of somatic cell lines fall into two classes: one seems to correspond to classical gene mutation, the other is characterized, albeit transiently, by karyotypic instability, high reversion frequency, and low plating efficiency. An interpretation of the origin of these drug-resistant mutants is offered on the basis of chromosomal variation, which generates variation of the number of copies of each individual chromosome and, consequently, of gene dosage.

Keywords: polymorphism, bromodeoxyuridine, thioguanine

Full text

PDF
5028

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albrecht A. M., Biedler J. L., Hutchison D. J. Two different species of dihydrofolate reductase in mammalian cells differentially resistant to amethopterin and methasquin. Cancer Res. 1972 Jul;32(7):1539–1546. [PubMed] [Google Scholar]
  2. Allderdice P. W., Miller O. J., Miller D. A., Warburton D., Pearson P. L., Klein G., Harris H. Chromosome analysis of two related heteroploid mouse cell lines by quinacrine fluorescence. J Cell Sci. 1973 Jan;12(1):263–274. doi: 10.1242/jcs.12.1.263. [DOI] [PubMed] [Google Scholar]
  3. Beaudet A. L., Roufa D. J., Caskey C. T. Mutations affecting the structure of hypoxanthine: guanine phosphoribosyltransferase in cultured Chinese hamster cells. Proc Natl Acad Sci U S A. 1973 Feb;70(2):320–324. doi: 10.1073/pnas.70.2.320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Breslow R. E., Goldsby R. A. Isolation and characterization of thymidine transport mutants of Chinese hamster cells. Exp Cell Res. 1969 Jun;55(3):339–346. doi: 10.1016/0014-4827(69)90567-9. [DOI] [PubMed] [Google Scholar]
  5. Chan V. L., Whitmore G. F., Siminovitch L. Mammalian cells with altered forms of RNA polymerase II. Proc Natl Acad Sci U S A. 1972 Nov;69(11):3119–3123. doi: 10.1073/pnas.69.11.3119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chasin L. A. The effect of ploidy on chemical mutagenesis in cultured Chinese hamster cells. J Cell Physiol. 1973 Oct;82(2):299–307. doi: 10.1002/jcp.1040820218. [DOI] [PubMed] [Google Scholar]
  7. Davidson R. L. Regulation of malanin synthesis in mammalian cells: effect of gene dosage on the expression of differentiation. Proc Natl Acad Sci U S A. 1972 Apr;69(4):951–955. doi: 10.1073/pnas.69.4.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fougère C., Ruiz F., Ephrussi B. Gene dosage dependence of pigment synthesis in melanoma x fibroblast hybrids (hamster cells-mouse fibroblast-DOPA-oxidase-irradiation). Proc Natl Acad Sci U S A. 1972 Feb;69(2):330–334. doi: 10.1073/pnas.69.2.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Francke U., Hammond D. S., Schneider J. A. The band patterns of twelve D 98-AH-2 marker chromosomes and their use for identification of intraspecific cell hybrids. Chromosoma. 1973;41(1):111–121. doi: 10.1007/BF00284079. [DOI] [PubMed] [Google Scholar]
  10. Green H., Wang R., Kehinde O., Meuth M. Multiple human TK chromosomes in human-mouse somatic cell hybrids. Nat New Biol. 1971 Dec 1;234(48):138–140. doi: 10.1038/newbio234138a0. [DOI] [PubMed] [Google Scholar]
  11. Harris M. Mutation rates in cells at different ploidy levels. J Cell Physiol. 1971 Oct;78(2):177–184. doi: 10.1002/jcp.1040780204. [DOI] [PubMed] [Google Scholar]
  12. Hashmi S., Allderdice P. W., Klein G., Miller O. J. Chromosomal heterogeneity in the RAG and MSWBS mouse tumor cell lines. Cancer Res. 1974 Jan;34(1):79–88. [PubMed] [Google Scholar]
  13. Hughes D. T. Cytogenetical polymorphism and evolution in mammalian somatic cell populations in vivo and vitro. Nature. 1968 Feb 10;217(5128):518–523. doi: 10.1038/217518a0. [DOI] [PubMed] [Google Scholar]
  14. LITTLEFIELD J. W. STUDIES ON THYMIDINE KINASE IN CULTURED MOUSE FIBROBLASTS. Biochim Biophys Acta. 1965 Jan 11;95:14–22. doi: 10.1016/0005-2787(65)90206-6. [DOI] [PubMed] [Google Scholar]
  15. LITTLEFIELD J. W. THE INOSINIC ACID PYROPHOSPHORYLASE ACTIVITY OF MOUSE FIBROBLASTS PARTIALLY RESISTANT TO 8-AZAGUANINE. Proc Natl Acad Sci U S A. 1963 Sep;50:568–573. doi: 10.1073/pnas.50.3.568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Littlefield J. W., Basilico C. Infection of thymidine kinase-deficient BHK cells with polyoma virus. Nature. 1966 Jul 16;211(5046):250–252. doi: 10.1038/211250a0. [DOI] [PubMed] [Google Scholar]
  17. Malawista S. E., Weiss M. C. Expression of differentiated functions in hepatoma cell hybrids: high frequency of induction of mouse albumin production in rat hepatoma-mouse lymphoblast hybrids. Proc Natl Acad Sci U S A. 1974 Mar;71(3):927–931. doi: 10.1073/pnas.71.3.927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mezger-Freed L. Puromycin resistance in haploid and heteroploid frog cells: gene or membrane determined? J Cell Biol. 1971 Dec;51(3):742–751. doi: 10.1083/jcb.51.3.742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miller O. J., Miller D. A., Allderdice P. W., Dev V. G., Grewal M. S. Quinacrine fluorescent karyotypes of human diploid and heteroploid cell lines. Cytogenetics. 1971;10(5):338–346. doi: 10.1159/000130152. [DOI] [PubMed] [Google Scholar]
  20. Morrow J., Colofiore J., Rintoul D. Azaguanine resistant hamster cell lines not deficient in hypoxanthine-guanine phosphoribosyl transferase. J Cell Physiol. 1973 Feb;81(1):97–100. doi: 10.1002/jcp.1040810112. [DOI] [PubMed] [Google Scholar]
  21. Orkin S. H., Littlefield J. W. Mutagenesis to aminopterin resistance in cultured hamster cells. Exp Cell Res. 1971 Nov;69(1):174–180. doi: 10.1016/0014-4827(71)90322-3. [DOI] [PubMed] [Google Scholar]
  22. Rothschild H., Black P. H. Effect of loss of thymidine kinase activity on the tumorigenicity of clones of SV40-transformed hamster cells. Proc Natl Acad Sci U S A. 1970 Oct;67(2):1042–1049. doi: 10.1073/pnas.67.2.1042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. SUBAK-SHARPE H. BIOCHEMICALLY MARKED VARIANTS OF THE SYRIAN HAMSTER FIBROBLAST CELL LINE BHK21 AND ITS DERIVATIVES. Exp Cell Res. 1965 Apr;38:106–119. doi: 10.1016/0014-4827(65)90432-5. [DOI] [PubMed] [Google Scholar]
  24. Sharp J. D., Capecchi N. E., Capecchi M. R. Altered enzymes in drug-resistant variants of mammalian tissue culture cells. Proc Natl Acad Sci U S A. 1973 Nov;70(11):3145–3149. doi: 10.1073/pnas.70.11.3145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shin S., Meera Khan P., Cook P. R. Characterization of hypoxanthine-guanine phosphoribosyl transferase in man--mouse somatic cell hybrids by an improved electrophoretic method. Biochem Genet. 1971 Feb;5(1):91–99. doi: 10.1007/BF00485734. [DOI] [PubMed] [Google Scholar]
  26. Terzi M. On the selection for the modal chromosome number in Chinese hamster cells. J Cell Physiol. 1972 Dec;80(3):359–365. doi: 10.1002/jcp.1040800306. [DOI] [PubMed] [Google Scholar]
  27. Thompson L. H., Baker R. M. Isolation of mutants of cultured mammalian cells. Methods Cell Biol. 1973;6:209–281. doi: 10.1016/s0091-679x(08)60052-7. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES