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. 1980 Nov;42(5):677–683. doi: 10.1038/bjc.1980.301

Cytotoxic effect in vivo of selected chemotherapeutic agents on synchronized murine fibrosarcoma cells.

D J Grdina, C P Sigdestad, L J Peters
PMCID: PMC2010549  PMID: 6161629

Abstract

The cytotoxic effects in vivo of single doses of either adriamycin (ADM), 1-beta-D-arabinofuranosylcytosine (Ara-C), bleomycin (BLM), cis-diamminedichloroplatinum (II) (cis-DDP), or cyclophosphamide (CY) on murine fibrosarcoma (FSa) cell populations were determined. Tumour cells were separated and synchronized by centrifugal elutriation. Viable tumour cells from selected elutriator fractions were then injected i.v. into whole-body-irradiated mice. Twenty minutes later selected doses of ADM, Ara-C, BLM, cis-DDP or CY were administered to selected groups of these animals. Fourteen days later the mice were killed. Killing of injected tumour cells by each of the chemotherapeutic agents was evidenced by a reduction in the lung cells by each of the chemotherapeutic agents was evidenced by a reduction in the lung colonies per cell injected in treated animals. Under these conditions the response of FSa cells in vivo to the 5 drugs tested differed both qualitatively and quantitatively. Ara-C was S-phase-specific in toxicity. ADM, BLM, and cis-DDP were preferentially toxic to S, G2+M and G1 cells respectively. CY, a drug requiring bioactivation to form alkylating metabolites, was found to be equally toxic to G1 and G2+M enriched populations, but less effective in killing cell populations enriched with early-S cells.

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Selected References

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

  1. Barranco S. C., Humphrey R. M. The effects of bleomycin on survival and cell progression in Chinese hamster cells in vitro. Cancer Res. 1971 Sep;31(9):1218–1223. [PubMed] [Google Scholar]
  2. Brock N., Hohorst H. J. Metabolism of cyclophosphamide. Cancer. 1967 May;20(5):900–904. doi: 10.1002/1097-0142(1967)20:5<900::aid-cncr2820200552>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  3. Donelli M. G., Bartosek I., Guaitani A., Martini A., Colombo T., Pacciarini M. A., Modica R. Importance of pharmacokinetic studies on cyclophosphamide (NSC-26271) in understanding its cytotoxic effect. Cancer Treat Rep. 1976 Apr;60(4):395–401. [PubMed] [Google Scholar]
  4. Drewinko B., Barlogie B. Age-dependent survival and cell-cycle progression of cultured cells exposed to chemotherapeutic drugs. Cancer Treat Rep. 1976 Dec;60(12):1707–1717. [PubMed] [Google Scholar]
  5. Drewinko B., Brown B. W., Gottlieb J. A. The effect of cis-diamminedichloroplatinum (II) on cultured human lymphoma cells and its therapeutic implications. Cancer Res. 1973 Dec;33(12):3091–3095. [PubMed] [Google Scholar]
  6. Fraval H. N., Roberts J. J. G1 phase chinese hamster V79-379A cells are inherently more sensitive to platinum bound to their DNA than mid S phase or asynchronously treated cells. Biochem Pharmacol. 1979 May 15;28(10):1575–1580. doi: 10.1016/0006-2952(79)90167-9. [DOI] [PubMed] [Google Scholar]
  7. Grdina D. J., Basic I., Mason K. A., Withers H. R. Radiation response of clonogenic cell populations separated from fibrosarcoma. Radiat Res. 1975 Sep;63(3):483–493. [PubMed] [Google Scholar]
  8. Grdina D. J., Peters L. J., Jones S., Chan E. Separation of cells from a murine fibrosarcoma on the basis of size. I. Relationship between cell size and age as modified by growth in vivo or in vitro. J Natl Cancer Inst. 1978 Jul;61(1):209–214. doi: 10.1093/jnci/61.1.209. [DOI] [PubMed] [Google Scholar]
  9. Grdina D. J., Peters L. J., Jones S., Chan E. Separation of cells from a murine fibrosarcoma on the basis of size. II. Differential effects of cell size and age on lung retention and colony formation in normal and preconditioned mice. J Natl Cancer Inst. 1978 Jul;61(1):215–220. doi: 10.1093/jnci/61.1.215. [DOI] [PubMed] [Google Scholar]
  10. Grdina D. J., Sigdestad C. P., Peters L. J. Phase-specific cytotoxicity in vivo of hydroxyurea on murine fibrosarcoma cells synchronized by centrifugal elutriation. Br J Cancer. 1979 Feb;39(2):152–158. doi: 10.1038/bjc.1979.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hill R. P., Bush R. S. A lung-colony assay to determine the radiosensitivity of cells of a solid tumour. Int J Radiat Biol Relat Stud Phys Chem Med. 1969 Jul;15(5):435–444. doi: 10.1080/09553006914550721. [DOI] [PubMed] [Google Scholar]
  12. Johnston D. A., White R. A., Barlogie B. Automatic processing and interpretation of DNA distributions: comparison of several techniques. Comput Biomed Res. 1978 Aug;11(4):393–404. doi: 10.1016/0010-4809(78)90020-4. [DOI] [PubMed] [Google Scholar]
  13. Kim S. H., Kim J. H. Lethal effect of adriamycin on the division cycle of HeLa cells. Cancer Res. 1972 Feb;32(2):323–325. [PubMed] [Google Scholar]
  14. Madoc-Jones H., Mauro F. Age responses to x rays, Vinca alkaloids, and hydroxyurea of murine lymphoma cells synchronized in vivo. J Natl Cancer Inst. 1970 Dec;45(6):1131–1143. [PubMed] [Google Scholar]
  15. Meyn R. E., Meistrich M. L., White R. A. Cycle-dependent anticancer drug cytotoxicity in mammalian cells synchronized by centrifugal elutriation. J Natl Cancer Inst. 1980 May;64(5):1215–1219. [PubMed] [Google Scholar]
  16. Momparler R. L. A model for the chemotherapy of acute leukemia with 1-beta-D-arabinofuranosylcytosine. Cancer Res. 1974 Aug;34(8):1775–1787. [PubMed] [Google Scholar]
  17. Skipper H. E., Schabel F. M., Jr, Wilcox W. S. Experimental evaluation of potential anticancer agents. XXI. Scheduling of arabinosylcytosine to take advantage of its S-phase specificity against leukemia cells. Cancer Chemother Rep. 1967 Jun;51(3):125–165. [PubMed] [Google Scholar]
  18. Suit H. D., Suchato C. Hyperbaric oxygen and radiotherapy of a fibrosarcoma and of a squamous-cell carcinoma of C3H mice. Radiology. 1967 Oct;89(4):713–719. doi: 10.1148/89.4.713. [DOI] [PubMed] [Google Scholar]
  19. Valeriote F., van Putten L. Proliferation-dependent cytotoxicity of anticancer agents: a review. Cancer Res. 1975 Oct;35(10):2619–2630. [PubMed] [Google Scholar]

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