Developmental defects in mice and rats treated postnatally with cytosine arabinoside

ICR Swiss albino mice and Sprague-Dawley rats were given cytosine arabinoside parenterally beginning at 1, 5, or 10 days of age. Animals were treated for 5 consecutive days at dosages ranging from 3.125 to 50 mg/kg/day. Numerous deaths and retardation of growth occurred in both species treated at higher dosages beginning at 1 day of age. Animals were examined histologically at 20 days of age. Cerebellar hypoplasia was especially marked in mice and rats treated beginning at 1 day of age. There was reduction in size of the cerebellum, with poorly delineated molecular, Purkinje cell, and internal granular layers. Retinal lesions were observed in both species, but were considerably more extensive in rats treated with cytosine arabinoside than in mice. Numerous rosettes were observed in the peripheral retina, with relative sparing of the central regions. Focal renal cortical dysplasia was also observed in animals treated beginning at 1 day of age. Autoradiographic studies indicated that significant cellular division occurs in the retina and renal cortex postnatally in both species. The significance of these studies with regard to the use of cytosine arabinoside in viral chemotherapy in newborn infants are yet to be determined.