Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1982 Aug;46(2):236–248. doi: 10.1038/bjc.1982.189

Sensitivity of normal mouse marrow and RIF-1 tumour to hyperthermia combined with cyclophosphamide or BCNU: a lack of therapeutic gain.

D J Honess, N M Bleehen
PMCID: PMC2011089  PMID: 6758828

Abstract

The effect of simultaneous whole-body heat (45 min 41 degrees C) on cyclophosphamide (CTX) and BCNU toxicity to normal mouse marrow stem cells and to the RIF-1 tumour in C3H/He mice has been studied. Marrow stem-cell survival was assayed by the spleen-colony technique at both 2 and 24 h after treatment, and also by following peripheral WBC count during the weeks after treatment. Heat potentiation of CTX toxicity to marrow stem cells was similar at both times and 24 h after treatment heat was dose-modifying with a DMF of 2.0. The heat potentiation of BCNU toxicity to stem cells was much greater at 24 h than at 2 h, and at 24 h had a DMF of 2.1. Peripheral WBC counts supported the results from 24 h assay for both drugs. RIF-1 tumour response was assayed by clonogenic cell survival measured 24 h after treatment, and by growth delay. For clonogenic tumour-cell survival after CTX, heated and unheated curves were parallel at doses above 75 mg/kg, yielding DMFs varying between 1.9 and 1.4 according to dose. DMFs for BCNU were also dose-dependent, lying between 2.0 and 1.6, the RIF-1 tumour being much less sensitive to BCNU than to CTX. Growth-delay data agreed with clonogenic cell survival. Therapeutic ratios for the combination of heat with CTX or BCNU fell in the range 0.91--0.69, according to dose, i.e. no gain or even therapeutic loss under the conditions of this study.

Full text

PDF
236

Selected References

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

  1. Begg A. C., Fu K. K., Kane L. J., Phillips T. L. Single-agent chemotherapy of a solid murine tumor assayed by growth delay and cell survival. Cancer Res. 1980 Jan;40(1):145–154. [PubMed] [Google Scholar]
  2. Brown C. H., 3rd, Carbone P. P. Effects of chemotherapeutic agents on normal mouse bone marrow grown in vitro. Cancer Res. 1971 Feb;31(2):185–190. [PubMed] [Google Scholar]
  3. Chrisman C. L., Baumgartner A. P. Micronuclei in bone-marrow cells of mice subjected to hyperthermia. Mutat Res. 1980 Jan;77(1):95–97. doi: 10.1016/0165-1218(80)90125-1. [DOI] [PubMed] [Google Scholar]
  4. Hellman S., Grate H. E. Effect of cyclophosphamide on the murine hematopoietic stem cell compartment as measured by different assay techniques. Blood. 1971 Dec;38(6):706–714. [PubMed] [Google Scholar]
  5. Hill S. A., Denekamp J. The response of six mouse tumours to combined heat and X rays: implications for therapy. Br J Radiol. 1979 Mar;52(615):209–218. doi: 10.1259/0007-1285-52-615-209. [DOI] [PubMed] [Google Scholar]
  6. Hume S. P., Robinson J. E., Hand J. W. The influence of blood flow on temperature distribution in the exteriorized mouse intestine during treatment by hyperthermia. Br J Radiol. 1979 Mar;52(615):219–222. doi: 10.1259/0007-1285-52-615-219. [DOI] [PubMed] [Google Scholar]
  7. Marmor J. B. Interactions of hyperthermia and chemotherapy in animals. Cancer Res. 1979 Jun;39(6 Pt 2):2269–2276. [PubMed] [Google Scholar]
  8. Rose W. C., Veras G. H., Laster W. R., Jr, Schabel F. M., Jr Evaluation of whole-body hyperthermia as an adjunct to chemotherapy in murine tumors. Cancer Treat Rep. 1979 Aug;63(8):1311–1325. [PubMed] [Google Scholar]
  9. Symonds R. P., Wheldon T. E., Clarke B., Bailey G. A comparison of the response to hyperthermia of murine haemopoietic stem cells (CFU-S) and L1210 leukaemia cells: enhanced killing of leukaemic cells in presence of normal marrow cells. Br J Cancer. 1981 Nov;44(5):682–691. doi: 10.1038/bjc.1981.254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. TILL J. E., McCULLOCH E. A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961 Feb;14:213–222. [PubMed] [Google Scholar]
  11. 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]
  12. Twentyman P. R., Kallman R. F., Brown J. M. The effect of time between X-irradiation and chemotherapy on the growth of three solid mouse tumors--I. Adriamycin. Int J Radiat Oncol Biol Phys. 1979 Aug;5(8):1255–1260. doi: 10.1016/0360-3016(79)90649-7. [DOI] [PubMed] [Google Scholar]
  13. Twentyman P. R., Morgan J. E., Donaldson J. Enhancement by hyperthermia of the effect of BCNU against the EMT6 mouse tumor. Cancer Treat Rep. 1978 Mar;62(3):439–443. [PubMed] [Google Scholar]
  14. Twentyman P. R. Sensitivity to cytotoxic agents of the EMT6 tumour in vivo: tumour volume versus in vitro plating. 1. Cyclophosphamide. Br J Cancer. 1977 Feb;35(2):208–217. doi: 10.1038/bjc.1977.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Twentyman P. R. Timing of assays: an important consideration in the determination of clonogenic cell survival both in vitro and in vivo. Int J Radiat Oncol Biol Phys. 1979 Aug;5(8):1213–1220. doi: 10.1016/0360-3016(79)90641-2. [DOI] [PubMed] [Google Scholar]
  16. Twentyman P. R., Yuhas J. M. Use of bacterial neutral protease for disaggregation of mouse tumours and multicellular tumor spheroids. Cancer Lett. 1980 May;9(3):225–228. doi: 10.1016/0304-3835(80)90091-9. [DOI] [PubMed] [Google Scholar]
  17. Valeriote F. A., Collins D. C., Bruce W. R. Hematological recovery in the mouse following single doses of gamma radiation and cyclophosphamide. Radiat Res. 1968 Mar;33(3):501–511. [PubMed] [Google Scholar]
  18. Van Putten L. M., Lelieveld P., Kram-Idsenga L. K. Cell-cycle specificity and therapeutic effectiveness of cytostatic agents. Cancer Chemother Rep. 1972 Dec;56(6):691–700. [PubMed] [Google Scholar]
  19. Wasserman T. H., Phillips T. L., Ross G., Kane L. J. Differential protection against cytotoxic chemotherapeutic effects on bone marrow CFUs by Wr-2721. Cancer Clin Trials. 1981;4(1):3–6. [PubMed] [Google Scholar]

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

RESOURCES