PREVENTION OF INSULIN-DEPENDENT DIABETES-MELLITUS BY 2'-DEOXYCOFORMYCIN IN THE BB WISTAR RAT

The effect of the adenosine deaminase (ADA) inhibitor 2'-deoxycoformyc in (dCF) on the development of insulin-dependent diabetes mellitus (ID DM) was assessed in the BB Wistar rat. Sixty-one male rats were treate d from days 30 to 120 with 0, 0.5, 1.0 or 1.5 mg dCF/kg/week. The inci dence of IDDM was 78% in the controls and was significantly (P < 0.01) decreased in rats receiving 1.5 mg dCF/kg/week (32%), but not in rats receiving lower doses of the drug. However, for those rats that becam e diabetic the mean time to the development of IDDM was unchanged in a nimals receiving dCF compared with control. dCF treatment did not prod uce significant weight loss in the animals or gross changes in the thy mus, spleen or kidneys. Although the protective effect of dCF against IDDM was likely produced by immunosuppression, the different dCF dosag es had similar effects on ADA suppression in spleen or thymus and on d ATP accumulation in these organs.