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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1992 Jul;83(7):789–793. doi: 10.1111/j.1349-7006.1992.tb01981.x

Myeloprotective Activity of Deoxyspergualin: Influence on Splenic Colony‐forming Cell Injury and Antitumor Activity of Mitomycin C in Mice

Kyuichi Nemoto 1, Yumi Sugawara 1, Miwa Ogino 1, Takako Mae 1, Fuminori Abe 1, Tomio Takeuchi 2
PMCID: PMC5918928  PMID: 1517153

Abstract

We have examined the efficacy of deoxyspergualin (DSG) in protecting splenic colony‐forming cells (CFU‐S) from mitomycin C (MMC)‐induced damage. The main findings of the study are as follows. (1) When DSG was administered at doses of 1.5 and 3 mg/kg for 7 days before the MMC injection, the decrease of the femoral CFU‐S caused by MMC was diminished on the day after the MMC injection. The optimal dose was found to be 3 mg/kg. (2) In animals receiving 3 mg/kg DSG for at least 3 days preceding the MMC injection, the femoral CFU‐S was more than 200% of that in the MMC alone group one day after the MMC injection. (3) The number of femoral CFU‐S in the mice which received 3 mg/kg DSG for 3 days prior to MMC was significantly restored day by day and reached 70% of normal at 5 days after the MMC injection, while it was only 13% of normal in the MMC alone group. Moreover, the prior DSG administration significantly diminished the MMC toxicity to circulating platelets. (4) DSG administration (3 mg/kg) 3 days prior to MMC did not weaken the antitumor activity against colon 26 adenocarcinoma or P388 leukemia when compared with MMC alone. These findings have shown the ability of DSG specifically to protect the animals against bone marrow toxicity caused by MMC without interfering with the antitumor activity.

Keywords: Key words, Deoxyspergualin, Hematopoietic cell, Mouse, Mitomycin C

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REFERENCES

  • 1. ) Nemoto , K. , Hayashi , M. , Abe , F. , Nakamura , T. , Ishizuka , M. and Umezawa , H.Immunosuppressive activities of 15‐deoxyspergualin in animals . J. Antibiot. , 40 , 561 – 562 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Nemoto , K. , Ito , J. , Abe , F. , Nakamura , T. , Takeuchi , T. and Umezawa , H.Suppression of humoral immunity in dogs by 15‐deoxyspergualin . J. Antibiot. , 40 , 1065 – 1066 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Nemoto , K. , Hayashi , M. , Ito , J. , Sugawara , Y. , Mae , T. , Fujii , H. , Abe , F. , Fujii , A. and Takeuchi , T.Deoxyspergualin in lethal murine graft‐versus‐host disease . Transplantation , 51 , 712 – 715 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Takeuchi , T. , Iinuma , H. , Kunimoto , S. , Masuda , T. , Ishizuka , M. , Takeuchi , M. , Hamada , M. , Naganawa , H. , Kondo , S. and Umezawa , H.A new antitumor antibiotic, spergualin: isolation and antitumor activity . J. Antibiot. , 34 , 1619 – 1621 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Amemiya , H. , Suzuki , S. , Ota , K. , Takahashi , K. , Sonoda , T. , Ishibashi , M. , Omoto , R. , Koyama , L. , Dohi , K. , Fukuda , Y. and Fukao , K.A novel rescue drug, 15‐deoxyspergualin. First clinical trial for recurrent graft rejection in renal recipients . Transplantation , 49 , 337 – 343 ( 1990. ). [PubMed] [Google Scholar]
  • 6. ) Takahashi , K. , Ota , K. , Tanabe , K. , Oba , S. , Teraoka , S. , Toma , H. , Agishi , T. , Kawaguchi , H. and Ito , K.Effect of a novel immunosuppressive agent, deoxyspergualin, on rejection in kidney transplant patients . Transplant. Proc , 22 , 1606 – 1612 ( 1990. ). [PubMed] [Google Scholar]
  • 7. ) Groth , C. G. , Ohlman , S. , Ericzon , B. G. , Barkholt , L. and Reinholt , F. P.Deoxyspergualin for liver graft rejection . Lancet , 336 , 626 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Nemoto , K. , Hayashi , M. , Sugawara , Y. , Abe , F. , Takita , T. and Takeuchi , T.Effect of deoxyspergualin on hematopoiesis: studies of murine hematopoietic progenitor cell and peripheral blood cell levels . J. Antibiot. , 42 , 312 – 316 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Nishimura , K. and Tokunaga , T.Effects of deoxyspergualin on the induction of cytotoxic T lymphocytes and bone marrow suppression . Transplant. Proc , 21 , 1104 – 1107 ( 1989. ). [PubMed] [Google Scholar]
  • 10. ) Umeda , Y. , Moriguchi , M. , Kuroda , H. , Nakamura , T. , Iinuma , H. , Takeuchi , T. and Umezawa , H.Synthesis and antitumor activity of spergualin analogues. I. Chemical modification of 7‐guanidino‐3‐hydroxyacyl moiety . J. Antibiot , 38 , 886 – 898 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Till , J. M. and McCulloch , E. A.A direct measurement of the radiation sensitivity of normal mouse bone marrow cells . Radial. Res. , 14 , 213 – 222 ( 1961. ). [PubMed] [Google Scholar]
  • 12. ) Plowman , J. , Harrison , S. D. , Trader , M. W. , Griswold , D. P. , Chad wick , M. , McComish , M. F. , Silveira , D. M. and Zaharko , D.P Technical antitumor activity and pharmacological properties of deoxyspergualin . Cancer Res. , 47 , 685 – 689 ( 1987. ). [PubMed] [Google Scholar]
  • 13. ) Nishikawa , K. , Shibasaki , C. , Hiratsuka , M. , Arakawa , M. , Takahashi , K. and Takeuchi , T.Antitumor spectrum of deoxyspergualin and its lack of cross‐resistance to other antitumor agents . J. Antibiot , 44 , 1101 – 1109 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Motoyoshi , K. , Takaku , F. , Maekawa , T. , Miura , Y. , Kimura , K. , Furusawa , S. , Hattori , M. , Nomura , T. , Mizoguchi , H. , Ogawa , M. , Kinugasa , K. , Tominaga , T. , Shimoyama , M. , Deura , K. , Ohta , K. , Taguchi , T. , Masaoka , T. and Kimura , I.Protective effect of partially purified human urinary colony‐stimulating factor on granulocytopenia after antitumor chemotherapy . Exp. Hematol. , 14 , 1069 – 1075 ( 1986. ). [PubMed] [Google Scholar]

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