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American Journal of Pathology, Vol 119, 65-72, Copyright © 1985 by American Society for Investigative Pathology

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

H Ratech, R Hirschhorn and GJ Thorbecke

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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