Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1986 Jun;53(6):753–759. doi: 10.1038/bjc.1986.129

Clonal variation in the sensitivity of a murine mammary carcinoma to melphalan.

T J McMillan, T C Stephens, G G Steel
PMCID: PMC2001408  PMID: 3718828

Abstract

The sensitivity to melphalan of clones derived from individual lung colonies produced by i.v. injection of cells of the MT murine mammary carcinoma (caMT) and its melphalan-resistant sub-line (MTME16) has been examined. A degree of clonal heterogeneity was observed which was greater than could be explained by experimental variation. The distribution of melphalan sensitivities in both wild-type caMT and MTME16 raises questions as to the validity of a two-compartment model of drug-resistance development in tumours. A more complex model, possibly involving a continuous spectrum of drug sensitivity, is required. Differences in the sensitivity of the clonal lines of wild-type caMT in various passages were observed and this would appear to be due to phenotypic instability in these lines. This suggests that to use survival data from clones which have been passaged many times for predicting the response of the parent tumour may be misleading.

Full text

PDF
753

Selected References

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

  1. Brouwer M., Smets L. A., Jongsma A. P. Isolation and characterization of subclones of L1210 murine leukemia with different sensitivities to various cytotoxic agents. Cancer Res. 1983 Jun;43(6):2884–2888. [PubMed] [Google Scholar]
  2. Calabresi P., Dexter D. L., Heppner G. H. Clinical and pharmacological implications of cancer cell differentiation and heterogeneity. Biochem Pharmacol. 1979 Jun 15;28(12):1933–1941. doi: 10.1016/0006-2952(79)90647-6. [DOI] [PubMed] [Google Scholar]
  3. Clements G. B. Selection of biochemically variant, in some cases mutant, mammalian cells in culture. Adv Cancer Res. 1975;21:273–390. doi: 10.1016/s0065-230x(08)60975-6. [DOI] [PubMed] [Google Scholar]
  4. Courtenay V. D. A soft agar colony assay for Lewis lung tumour and B16 melanoma taken directly from the mouse. Br J Cancer. 1976 Jul;34(1):39–45. doi: 10.1038/bjc.1976.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goldie J. H., Coldman A. J. A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep. 1979 Nov-Dec;63(11-12):1727–1733. [PubMed] [Google Scholar]
  6. Gunduz N. Cytokinetics of tumour and endothelial cells and vascularization of lung metastases in C3H/He mice. Cell Tissue Kinet. 1981 Jul;14(4):343–363. doi: 10.1111/j.1365-2184.1981.tb00542.x. [DOI] [PubMed] [Google Scholar]
  7. Heppner G. H., Dexter D. L., DeNucci T., Miller F. R., Calabresi P. Heterogeneity in drug sensitivity among tumor cell subpopulations of a single mammary tumor. Cancer Res. 1978 Nov;38(11 Pt 1):3758–3763. [PubMed] [Google Scholar]
  8. McMillan T. J., Stephens T. C., Steel G. G. Development of drug resistance in a murine mammary tumour. Br J Cancer. 1985 Dec;52(6):823–832. doi: 10.1038/bjc.1985.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Neri A., Nicolson G. L. Phenotypic drift of metastatic and cell-surface properties of mammary adenocarcinoma cell clones during growth in vitro. Int J Cancer. 1981 Dec;28(6):731–738. doi: 10.1002/ijc.2910280612. [DOI] [PubMed] [Google Scholar]
  10. Poste G., Doll J., Fidler I. J. Interactions among clonal subpopulations affect stability of the metastatic phenotype in polyclonal populations of B16 melanoma cells. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6226–6230. doi: 10.1073/pnas.78.10.6226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Poste G. Experimental systems for analysis of the malignant phenotype. Cancer Metastasis Rev. 1982;1(2):141–199. doi: 10.1007/BF00048224. [DOI] [PubMed] [Google Scholar]
  12. Skipper H. E., Schabel F. M., Jr, Lloyd H. H. Experimental therapeutics and kinetics: selection and overgrowth of specifically and permanently drug-resistant tumor cells. Semin Hematol. 1978 Jul;15(3):207–219. [PubMed] [Google Scholar]
  13. Stephens T. C., Currie G. A., Peacock J. H. Repopulation of gamma-irradiated Lewis lung carcinoma by malignant cells and host macrophage progenitors. Br J Cancer. 1978 Nov;38(5):573–582. doi: 10.1038/bjc.1978.252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Stephens T. C., Peacock J. H. Clonal variation in the sensitivity of B16 melanoma to m-AMSA. Br J Cancer. 1982 Jun;45(6):821–829. doi: 10.1038/bjc.1982.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Welch D. R., Evans D. P., Tomasovic S. P., Milas L., Nicolson G. L. Multiple phenotypic divergence of mammary adenocarcinoma cell clones. II. Sensitivity to radiation, hyperthermia and FUdR. Clin Exp Metastasis. 1984 Oct-Dec;2(4):357–371. doi: 10.1007/BF00135173. [DOI] [PubMed] [Google Scholar]
  16. Welch D. R., Krizman D. B., Nicolson G. L. Multiple phenotypic divergence of mammary adenocarcinoma cell clones. I. In vitro and in vivo properties. Clin Exp Metastasis. 1984 Oct-Dec;2(4):333–355. doi: 10.1007/BF00135172. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES