Selective immunotoxic effects in mice treated with the adenosine deaminase inhibitor 2'-deoxycoformycin.
Mice were administered the adenosine deaminase inhibitor 2'-deoxycoformycin by daily intraperitoneal injection for five days and evaluated 24 h, 72 h and 6 days after the final dose. Spleen weight was decreased in treated mice for up to 6 days after treatment whereas body weight was significantly affected only at 24 h in mice administered 4 micrograms 2'-deoxycoformycin/g of body weight. The number and relative percentage of circulating lymphocytes were decreased 24 and 72 h after the last injection. Lymphoproliferative responses to T cell mitogens were suppressed for at least 72 h post-treatment whereas the mixed lymphocyte response was normal at 24 h but was depressed at 72 h post-treatment. Conversely, natural killer cell activity was greater in treated mice than in controls for the entire observation period. Data from cell surface marker analysis provided indirect evidence that natural killer effector cells lack sensitivity to 2'-deoxycoformycin. The antibody responses of mice treated with 2 or 4 micrograms 2'-deoxycoformycin/g over four days prior to or after immunization with sheep erythrocytes were suppressed or enhanced, respectively, compared to controls. These results indicate selective effects of 2'-deoxycoformycin on immune function and suggest that subpopulations of lymphocytes differ in the degree of sensitivity to 2'-deoxycoformycin.
D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000954:Antigens, Surface / Q000032:analysis; D001772:Blood Cell Count / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D005260:Female; D007109:Immunity / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D009929:Organ Size / Q000187:drug effects; D015649:Pentostatin; D012263:Ribonucleosides / Q000494:pharmacology*; D013154:Spleen / Q000276:immunology
D058892:Adenosine Deaminase Inhibitors; D000954:Antigens, Surface; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; D009700:Nucleoside Deaminases