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. 1985 Apr;119(1):65–72.

Effects of deoxycoformycin in mice. III. A murine model reproducing multi-system pathology of human adenosine deaminase deficiency.

H Ratech, R Hirschhorn, G J Thorbecke
PMCID: PMC1888086  PMID: 3872599

Abstract

Adult AKR/J mice were treated with 10 micrograms/g or 100 micrograms/g 2'-deoxycoformycin, an adenosine deaminase inhibitor with chemotherapeutic potential. The thymus and adrenal glands were decreased in weight more than any other organ. Histologic and cytofluorographic analyses indicated preferential depletion of peanut-agglutinin-positive, cortical thymocytes, as well as acute, dose-dependent damage to the adrenal cortex and medulla. The effect of 2'-deoxycoformycin on the thymus was proven to be independent of the adrenal glands by use of adrenalectomized mice. Dose-dependent liver necrosis, hemolysis, and leukemoid reactivity were observed. These findings illustrate a differential sensitivity of thymocyte subpopulations and suggest, in addition, preferential sensitivity of certain nonlymphoid tissues to 2'-deoxycoformycin administered in vivo.

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Selected References

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

  1. Coleman M. S., Donofrio J., Hutton J. J., Hahn L., Daoud A., Lampkin B., Dyminski J. Identification and quantitation of adenine deoxynucleotides in erythrocytes of a patient with adenosine deaminase deficiency and severe combined immunodeficiency. J Biol Chem. 1978 Mar 10;253(5):1619–1626. [PubMed] [Google Scholar]
  2. RUSSELL E. S., NEUFELD E. F., HIGGINS C. T. Comparison of normal blood picture of young adults from 18 inbred strains of mice. Proc Soc Exp Biol Med. 1951 Dec;78(3):761–766. doi: 10.3181/00379727-78-19210. [DOI] [PubMed] [Google Scholar]
  3. Ramboer C., Piessens F., De Groote J. Serum xanthine oxidase and liver disease. Digestion. 1972;7(3):183–195. doi: 10.1159/000197273. [DOI] [PubMed] [Google Scholar]
  4. Ratech H., Bell M. K., Hirschhorn R., Thorbecke G. J. Effects of deoxycoformycin in mice. I. Suppression and enhancement of in vivo antibody responses to thymus-dependent and -independent antigens. J Immunol. 1984 Jun;132(6):3071–3076. [PubMed] [Google Scholar]
  5. Ratech H., Thorbecke G. J., Hirschhorn R. Metabolic abnormalities of human adenosine deaminase deficiency reproduced in the mouse by 2'-deoxycoformycin, and adenosine deaminase inhibitor. Clin Immunol Immunopathol. 1981 Oct;21(1):119–127. doi: 10.1016/0090-1229(81)90200-2. [DOI] [PubMed] [Google Scholar]
  6. Reisner Y., Linker-Israeli M., Sharon N. Separation of mouse thymocytes into two subpopulations by the use of peanut agglutinin. Cell Immunol. 1976 Jul;25(1):129–134. doi: 10.1016/0008-8749(76)90103-9. [DOI] [PubMed] [Google Scholar]
  7. Siaw M. F., Mitchell B. S., Koller C. A., Coleman M. S., Hutton J. J. ATP depletion as a consequence of adenosine deaminase inhibition in man. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6157–6161. doi: 10.1073/pnas.77.10.6157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Smith C. M., Belch A., Henderson J. F. Hemolysis in mice treated with deoxycoformycin, an inhibitor of adenosine deaminase. Biochem Pharmacol. 1980 Apr 15;29(8):1209–1210. doi: 10.1016/0006-2952(80)90421-9. [DOI] [PubMed] [Google Scholar]
  9. Smyth J. F., Young R. C., Young D. M. In vivo toxicity to lymphoid tissue by 2'-deoxycoformycin. Cancer Chemother Pharmacol. 1978;1(1):49–51. doi: 10.1007/BF00253146. [DOI] [PubMed] [Google Scholar]
  10. Sordillo E. M., Ikehara S., Good R. A., Trotta P. P. Immunosuppression by 2' deoxycoformycin: studies on the mode of administration. Cell Immunol. 1981 Sep 15;63(2):259–271. doi: 10.1016/0008-8749(81)90005-8. [DOI] [PubMed] [Google Scholar]
  11. Spremulli E., Crabtree G. W., Dexter D. L., Diamond I., Calabresi P. 2'-Deoxycoformycin-induced hemolysis in the mouse. J Natl Cancer Inst. 1982 Jun;68(6):1011–1014. [PubMed] [Google Scholar]
  12. Tedde A., Balis M. E., Ikehara S., Pahwa R., Good R. A., Trotta P. P. Animal model for immune dysfunction associated with adenosine deaminase deficiency. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4899–4903. doi: 10.1073/pnas.77.8.4899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Tedde A., Balis M. E., Schonberg R., Trotta P. P. Effects of 2'-deoxycoformycin infusion on mouse adenosine deaminase. Cancer Res. 1979 Aug;39(8):3044–3050. [PubMed] [Google Scholar]
  14. Valentine W. N., Paglia D. E., Tartaglia A. P., Gilsanz F. Hereditary hemolytic anemia with increased red cell adenosine deaminase (45- to 70-fold) and decreased adenosine triphosphate. Science. 1977 Feb 25;195(4280):783–785. doi: 10.1126/science.836588. [DOI] [PubMed] [Google Scholar]

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