Effects of cytosine arabinoside on in vivo and in vitro mouse limb development

Summary When pregnant mice were exposed to 40 mg per kg of cytosine arabinoside (ara-C) on days 10 to 12 of gestation, adactylous limbs with large, distally located blisters were found when the fetuses were examined on day 18. Embryonic limbs exposed transplacentally under identical conditions and explanted to culture exhibited the same morphological abnormality as did limbs exposed directly in culture to 0.1 to 1 μg per ml of ara-C. Two noncytotoxic analogues of ara-C, uridine arabinoside (ara-U) and hypoxanthine arabinoside (ara-HX), had no influence on morphological differentiation of limbs in vitro. Ara-C alone caused a dose-related decrease in uptake of³H-thymidine and³⁵SO₄ in cultured limb buds. Production of this morphologically distinct malformation in vitro will allow detailed biochemical investigations on the effect of ara-C limb ectodermal-mesenchymal interactions. Supported by NIH Postdoctoral Fellowship No. CM02660. Supported by NIEHS Predoctoral Fellowship No. ES00127. Supported by NIEHS Toxicology Training Grant No. ES00127.