Teratogenic effects of the pyrimidine analogues 5‐lododeoxyuridine and cytosine arabinoside in late fetal mice and rats

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Abstract
Pregnant mice and rats were treated daily with 5‐iododeoxyuridine (IUDR) or cytosine arabinoside (CA) on 3 consecutive days, beginning on day 16 and 18 of pregnancy, respectively. Offspring were killed at 10 and 20 days of age and the cerebellum, eye, and kidney examined histologically. All offspring of mice treated with 400 mg/kg IUDR were stillborn or died within the first 48 h of life, and deaths occurred at other dosages in both species. In IUDR‐exposed mice and rats there was persistence of granule cells in the external granular layer, and scattered foci of microcystic tubular change in the renal cortices. In both species CA produced segmental cerebellar hypoplasia and focal microcystic renal cortical dysplasia. Retinal dysplasia occurred in rats exposed to 50 mg/kg. Lesions were concentrated in the central retina, corresponding with the stage of development at the time of administration of CA. The teratogenic effects of IUDR were minimal and were induced by dosages much higher than normally used in human medicine. On the other hand, lesions were more extensive in mice and rats exposed to CA. Thus, in addition to other known causes of congenital retinal dysplasia, defective development may be drug induced, in this case by the prenatal administration of CA.