Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1984 Aug;50(2):153–158. doi: 10.1038/bjc.1984.157

Patterns of cross-sensitivity in the responses of clonal subpopulations isolated from the RIF-1 mouse sarcoma to selected nitrosoureas and nitrogen mustards.

J G Reeve, K A Wright, P Workman
PMCID: PMC1976874  PMID: 6466534

Abstract

The response of clonal subpopulations isolated from the RIF-1 mouse sarcoma to melphalan treatment is independent of cell ploidy, whereas a clear relationship exists between ploidy and cell sensitivity to CCNU treatment. In the present study RIF-1 clones have been exposed to nitrogen mustard, aniline mustard and chlorambucil, and to nitrosoureas BCNU, MeCCNU and chlorozotocin, in order to evaluate whether or not the different physiochemical and biological activities of these agents would affect the patterns of drug sensitivity obtained for melphalan and CCNU. Irrespective of the different lipophilicities, transport properties and chemical reactivities of the nitrogen mustards, RIF-1 clones showed the same pattern of sensitivity as previously observed for melphalan. Similarly, RIF-1 clones when exposed to nitrosoureas BCNU, MeCCNU and chlorozotocin, showed the same pattern of sensitivity as that obtained for CCNU exposure. These data suggest (a) that the variation in the sensitivity of RIF-1 clones to treatment by the nitrogen mustards is unlikely to reflect differences in either membrane permeability or in drug transport and (b) that the ploidy dependent nitrosourea responses shown by RIF-1 clones similarly do not reflect differences in drug uptake.

Full text

PDF
153

Selected References

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

  1. Begleiter A., Goldenberg G. J. Uptake and decomposition of chlorambucil by L5178Y lymphoblasts in vitro. Biochem Pharmacol. 1983 Feb 1;32(3):535–539. doi: 10.1016/0006-2952(83)90535-x. [DOI] [PubMed] [Google Scholar]
  2. Begleiter A., Grover J., Froese E., Goldenberg G. J. Membrane transport, sulfhydryl levels and DNA cross-linking in Chinese hamster ovary cell mutants sensitive and resistant to melphalan. Biochem Pharmacol. 1983 Jan 15;32(2):293–300. doi: 10.1016/0006-2952(83)90558-0. [DOI] [PubMed] [Google Scholar]
  3. Begleiter A., Lam H. P., Goldenberg G. J. Mechanism of uptake of nitrosoureas by L5178Y lymphoblasts in vitro. Cancer Res. 1977 Apr;37(4):1022–1027. [PubMed] [Google Scholar]
  4. Bruce W. R., Meeker B. E., Valeriote F. A. Comparison of the sensitivity of normal hematopoietic and transplanted lymphoma colony-forming cells to chemotherapeutic agents administered in vivo. J Natl Cancer Inst. 1966 Aug;37(2):233–245. [PubMed] [Google Scholar]
  5. Crathorn A. R., Roberts J. J. Mechanism of the cytotoxic action of alkylating agents in mammalian cells and evidence for the removal of alkylated groups from deoxyribonucleic acid. Nature. 1966 Jul 9;211(5045):150–153. doi: 10.1038/211150a0. [DOI] [PubMed] [Google Scholar]
  6. Elliott E. M., Ling V. Selection and characterization of Chinese hamster ovary cell mutants resistant to melphalan (L-phenylalanine mustard). Cancer Res. 1981 Feb;41(2):393–400. [PubMed] [Google Scholar]
  7. Erickson L. C., Laurent G., Sharkey N. A., Kohn K. W. DNA cross-linking and monoadduct repair in nitrosourea-treated human tumour cells. Nature. 1980 Dec 25;288(5792):727–729. doi: 10.1038/288727a0. [DOI] [PubMed] [Google Scholar]
  8. Goldenberg G. J., Vanstone C. L., Bihler I. Transport of nitrogen mustard on the transport-carrier for choline in L5178Y lymphoblasts. Science. 1971 Jun 11;172(3988):1148–1149. doi: 10.1126/science.172.3988.1148. [DOI] [PubMed] [Google Scholar]
  9. Goldenberg G. J., Vanstone C. L., Israels L. G., Iise D., Bihler I. Evidence for a transport carrier of nitrogen mustard in nitrogen mustard-sensitive and -resistant L5178Y lymphoblasts. Cancer Res. 1970 Sep;30(9):2285–2291. [PubMed] [Google Scholar]
  10. HIRONO I. Non-protein sulphydryl group in the original strain and sub-line of the ascites tumour resistant to alkylating reagents. Nature. 1960 Jun 25;186:1059–1060. doi: 10.1038/1861059a0. [DOI] [PubMed] [Google Scholar]
  11. Redwood W. R., Colvin M. Transport of melphalan by sensitive and resistant L1210 cells. Cancer Res. 1980 Apr;40(4):1144–1149. [PubMed] [Google Scholar]
  12. Reeve J. G., Twentyman P. R. Clonal variation in the arrest, survival and growth of RIF-1 mouse sarcoma cells in the lungs of C3H mice. Br J Cancer. 1983 Jun;47(6):833–840. doi: 10.1038/bjc.1983.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Reeve J. G., Wright K. A., Twentyman P. R. Response to X-radiation and cytotoxic drugs of clonal subpopulations of different ploidy and metastatic potential isolated from RIF-1 mouse sarcoma. Br J Cancer. 1983 Jun;47(6):841–848. doi: 10.1038/bjc.1983.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Roberts J. J., Crathorn A. R., Brent T. P. Repair of alkylated DNA in mammalian cells. Nature. 1968 Jun 8;218(5145):970–972. doi: 10.1038/218970a0. [DOI] [PubMed] [Google Scholar]
  15. Twentyman P. R., Brown J. M., Gray J. W., Franko A. J., Scoles M. A., Kallman R. F. A new mouse tumor model system (RIF-1) for comparison of end-point studies. J Natl Cancer Inst. 1980 Mar;64(3):595–604. [PubMed] [Google Scholar]
  16. Wheeler G. P., Bowdon B. J., Grimsley J. A., Lloyd H. H. Interrelationships of some chemical, physicochemical, and biological activities of several 1-(2-haloethyl)-1-nitrosoureas. Cancer Res. 1974 Jan;34(1):194–200. [PubMed] [Google Scholar]
  17. Workman P., Double J. A., Wilman D. E. Enzyme activated anti-tumour agents--III. Hydrolysis of conjugates of p-hydroxyaniline mustard in aqueous solution. Biochem Pharmacol. 1976 Nov 1;25(21):2347–2350. doi: 10.1016/0006-2952(76)90026-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES