High incidence of neoplasms in female NZB/NZW mice treated with pulse doses of cyclophosphamide.
The immunosuppressive properties of cyclophosphamide prevent formation of anti-DNA antibodies and prolong lifespans in autoimmune NZB/NZW mice, an animal model of systemic lupus erythematosus. In the current study, NZB/NZW mice were treated with weekly doses of cyclophosphamide to determine if intermittent pulses of the drug were effective therapy. Life-long treatment with cyclophosphamide, 56 mg/kg/week, was started at the mean age of 6 weeks; results were compared with saline-injected control mice. Pulse therapy with cyclophosphamide suppressed anti-DNA antibody levels, prevented severe glomerulonephritis and prolonged longevity. Seventeen of 19 treated mice developed neoplasms; 7 of these immunosuppressed animals had 2 to 4 separate neoplasms. Examination of earlier studies in this laboratory in which NZB/NZW mice were treated each day with cyclophosphamide showed that daily and weekly therapeutic regimens had similar immunosuppressive and oncogenic effects.
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000662:veterinary*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005921:Glomerulonephritis / Q000188:drug therapy / Q000662:veterinary; D007165:Immunosuppression Therapy / Q000662:veterinary; D008136:Longevity; D051379:Mice; D008815:Mice, Inbred Strains; D009369:Neoplasms / Q000453:epidemiology / Q000662:veterinary*; D012376:Rodent Diseases / Q000188:drug therapy* / Q000453:epidemiology; D014657:Vasculitis / Q000188:drug therapy / Q000662:veterinary
D000974:Antibodies, Antinuclear; D003520:Cyclophosphamide