Skip to main content
NCBI home page
Journal of Cancer Research and Clinical Oncology logoLink to Journal of Cancer Research and Clinical Oncology
. 1992 Mar;118(3):171–175. doi: 10.1007/BF01410129

The additive effect ofα-difluoromethylornithine (DFMO) and radiation therapy on a rat glioma model

Takashi Tsukahara 1,✉, Masaru Tamura 1, Hiromichi Yamazaki 1, Hideyuki Kurihara 1, Shigeru Matsuzaki 3
PMCID: PMC12201616  PMID: 1548280

Abstract

The effects of α-difluoromethylornithine (DFMO), radiation and the therapy of their combination were investigated in rats bearing G-XII glioma. DFMO treatment as well as radiation therapy prolonged the survival period when compared to the results in non-treated control rats. The combination therapy showed a greater effect on the survival rate than the single therapies, the effect being additive. The concentration of putrescine, spermidine, andN 1-acetylspermidine in tumor tissues was lowered by DFMO, while that of spermine was slightly elevated. Radiation decreased the concentration of all the polyamines, putrescine, spermidine, spermine andN 1-acetylspermidine. The concomitant treatment with DFMO and radiation further decreased the concentrations of putrescine andN 1-acetylspermidine in tumor tissues. The survival period of glioma-bearing rats is inversely correlated with the tissue levels of putrescine plusN 1-acetylspermidine.

Key words: α-Difluoromethylornithine, Radiation therapy, Polyamines, Rat glioma

Abbreviations

DFMO

α-difluoromethylornithine

BrdUrd

bromodeoxyuridine

References

  1. Deen DF, Tofilon PJ (1984) Combined effect of drugs and radiation against tumor cells. In: Rosenblum ML, Wilson CB (eds) Progress in experimental tumor research, vol 28. Brain tumor therapy. Karger, Basel, pp 183–197 [DOI] [PubMed] [Google Scholar]
  2. Eklint MM (1977) Fundamental questions in the combined use of radiation and chemicals in the treatment of cancer. J Radiat Oncol Phys 5:1711–1720 [DOI] [PubMed] [Google Scholar]
  3. Harik SI, Sutton CH (1979) Putrescine as a biochemical marker of malignant brain tumor. Cancer Res 39:5010–5015 [PubMed] [Google Scholar]
  4. Heby O, Marton LJ, Wilson CB, Martinetz HM (1975) Polyamine metabolism in a rat brain tumor cell line: its relationship to the growth rate. J Cell Physiol 86:511–522 [DOI] [PubMed] [Google Scholar]
  5. Hoshino T, Nagashima T, Murovic JA, Wilson CB, Edwards MSB, Gutin PH, Davis RL, Dearmond SJ (1986) In situ cell kinetics studies on human neuroectodermal tumors with bromodeoxyuridine labeling. J Neurosurg 64:453–459 [DOI] [PubMed] [Google Scholar]
  6. Levin VA, Chamberlain MC, Prados MD, Choucair AK, Berger MS, Silver P, Seager M, Gutin PH, Davis RL, Wilson CB (1987) Phase I–II study of eflornithine and mitoguazone combined in the treatment of recurrent primary brain tumors. Cancer Treat Rep 71:459–464 [PubMed] [Google Scholar]
  7. Marton LJ, Levin VA, Hervatin SJ, Koch-Weser J, McCann PP, Sjoerdsma A (1981) Potentiation of the antitumor therapeutic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea by α-difluoromethylornithine, an ornithine decarboxylase inhibitor. Cancer Res 41:4426–4431 [PubMed] [Google Scholar]
  8. Matsuzaki S, Hamana K, Imai K, Matsuura K (1982) Occurrence in high concentration ofN1-acetylspermidine andsym-homospermidine in the hamster epididymis. Biochem Biophys Res Commun 107:307–313 [DOI] [PubMed] [Google Scholar]
  9. Mennel HD, Groneck P (1977) Quantitative aspects of transplantation of experimentally induced tumors of the nervous system. Acta Neuropathol (Berl) 40:145–150 [DOI] [PubMed] [Google Scholar]
  10. Metcalf BW, Bey P, Danzin C, Jung MJ, Casara P, Vevert JP (1978) Catalytic irreversible inhibition of mammalian ornithine decarboxylase (E.C.4.1.1.17) by substrate and product analogues. J Am Chem Soc 100:2551–2553 [Google Scholar]
  11. Oldendorf WH (1974) Blood-brain barrier permeability to drugs. Annu Rev Pharmacol 14:239–248 [Google Scholar]
  12. Oredsson SM, Marton LJ (1984) Potential use of polyamine biosynthesis inhibitors in tumor therapy. In: Rosenblum ML, Wilson CB (eds) Progress in tumor research, vol 28. Brain tumor therapy. Karger, Basel, pp 102–117 [DOI] [PubMed] [Google Scholar]
  13. Prakash NJ, Schechter PJ, Grove J, Koch-Weser J (1978) Effect of α-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ornithine decarboxylase, on L1210 leukemia in mice. Cancer Res 38:3059–3062 [PubMed] [Google Scholar]
  14. Prakash NJ, Shechter PJ, Mamont PS, Grove J, Koch-Weser J, Sjoerdsma A (1980) Inhibition of EMT6 tumor growth by interference with polyamine biosynthesis; effects of α-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase. Life Sci 26:181–184 [DOI] [PubMed] [Google Scholar]
  15. Shapiro WR (1974) The chemotherapy of intracerebral vs subcutaneous murine gliomas. Arch Neurol 30:222–226 [DOI] [PubMed] [Google Scholar]
  16. Shapiro JR, Shapiro WR (1984) Clonal tumor cell heterogeneity. In: Rosenblum ML, Wilson CB (eds) Progress in experimental tumor research, vol 27. Brain tumor biology. Karger, Basel, pp 49–66 [PubMed] [Google Scholar]
  17. Seidenfeld J, Deen DF, Marton LJ (1980) Depletion of intracellular polyamine content does not alter the survival of 9L rat brain tumor cells after X-irradiation. Int J Radiat Biol 38:223–229 [DOI] [PubMed] [Google Scholar]
  18. Seidenfeld J, Gray JW, Marton LJ (1981) Depletion of 9L rat brain tumor cell polyamine content by treatment withDl-α-difluoromethylornithine inhibits proliferation and G1 to S transition. Exp Cell Res 131:209–216 [DOI] [PubMed] [Google Scholar]
  19. Takenoshita S, Matsuzaki S, Nakano G, Kimura H, Hoshi H, Shoda H, Nakamura T (1984) Selective elevation of theN1-acetylspermidine level in human colorectal adenocarcinomas. Cancer Res 44:845–847 [PubMed] [Google Scholar]
  20. Tamura M, Mennel HD, Zülch KJ (1979) Brain tumor chemotherapy using a rat glioma model. J Cancer Res Clin Oncol 94:39–46 [DOI] [PubMed] [Google Scholar]
  21. Tamura M, Inoue H, Koizumi H, Nakamura M, Yonome I, Niibe H (1985) Radiation therapy of rat brain tumor using misonidazole as hypoxic cell sensitizer. J Cancer Res Clin Oncol 109:188–192 [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tamura M, Kunimine H, Zama A, Tamaki Y, Niibe H (1988) Effect of hyperthermia in combination with radiation therapy in a rat glioma model. No Shinkei Geka 16:659–663 [PubMed] [Google Scholar]
  23. Vick NA, Khandekar JD, Binger DD (1977) Chemotherapy of brain tumors—the “blood-brain barrier” is not a factor. Arch Neurol 34:523–526 [DOI] [PubMed] [Google Scholar]
  24. Yamazaki H, Tsukahara T, Uki J, Matsuzaki S (1986) Elevated levels of free putrescine andN1-acetylspermidine in cyst fluids of malignant brain tumors. J Neurol Neurosurg Psychiatry 49:209–210 [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Cancer Research and Clinical Oncology are provided here courtesy of Springer

RESOURCES