Morphologic changes and immunohistochemical localization of adenosine deaminase in tissues of rats given injections of 2'-deoxycoformycin.
2'-Deoxycoformycin (DCF) is a potent inhibitor of adenosine deaminase (ADA) and a potential antineoplastic and immunosuppressive agent. In this study the kinetics of ADA expression was assessed by immunomorphologic and enzymatic methods in tissues of ACI rats given injections of DCF. The rats received a daily ip injection of 10 mg DCF/kg for 3 consecutive days. This treatment destroyed cortical thymocytes, whereas lymphocytes of the thymic medulla were mainly preserved. In control phosphate-buffered saline-injected rats, cortical thymocytes were not affected morphologically and displayed strong ADA staining. It was found unexpectedly that injections of DCF produced activation and, possibly, differentiation of B-cells in the mesenteric lymph nodes and spleen. These activated B-lymphocytes and plasma cells stained strongly for ADA. Transient changes in patterns of ADA expression were also observed in endothelial cells of blood vessels and liver Kupffer's cells, but these changes were not accompanied by degeneration of the cells. The treatment with DCF did not result in any permanent abnormalities in the rat tissues.
D000243:Adenosine Deaminase / Q000032:analysis*; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004386:Duodenum / Q000201:enzymology; D005260:Female; D006651:Histocytochemistry; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000201:enzymology; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D009504:Neutrophils / Q000201:enzymology; D009700:Nucleoside Deaminases / Q000032:analysis*; D015649:Pentostatin; D010950:Plasma Cells / Q000201:enzymology; D051381:Rats; D011912:Rats, Inbred ACI; D012263:Ribonucleosides / Q000494:pharmacology*; D013154:Spleen / Q000201:enzymology; D013950:Thymus Gland / Q000187:drug effects / Q000201:enzymology*; D013997:Time Factors
D058892:Adenosine Deaminase Inhibitors; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase