Effects of deoxycoformycin in mice. III. A murine model reproducing multi-system pathology of human adenosine deaminase deficiency.
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.
D000243:Adenosine Deaminase / Q000172:deficiency*; D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004195:Disease Models, Animal; D004906:Erythrocyte Count; D005260:Female; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008806:Mice, Inbred AKR; D009700:Nucleoside Deaminases / Q000172:deficiency*; D009929:Organ Size / Q000187:drug effects; D015649:Pentostatin; D012263:Ribonucleosides / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology
D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase