Effects of 5-Fluorouracil and Cytosine Arabinoside on the Manifestation of Digital Malformations in Pdn Mice

Abstract

It is known that in mice and rats 5-fluorouracil (5-FU) or cytosine arabinoside (Ara-C) induce malformations of digits including preaxial polydactyly. Pdn/Pdn fetuses show preaxial polydactyly of duplicated or triplicated metacarpal/ metatarsal type in the fore- and hindlimbs. Pdn/+ offspring have one extra-digit preaxially in the hindlimb. When treated with subteratogenic dose of 5-FU on day 10 of gestation, the extra metatarsals of Pdn/Pdn decreased in number, and preaxial polydactyly of distal phalangeal type changed to that of proximal phalangeal type in Pdn/+. When treated with teratogenic doses of 5-FU or Ara-C on day 10, the number of extra digits decreased and even preaxial oligodactyly was observed in Pdn/Pdn, while preaxial polydactyly of metacarpal/metatarsal type appeared in Pdn/+ and +/+. When treated with teratogenic doses of 5-FU or Ara-C on day 11 , extra digits of the preaxial side decreased in number and preaxial oligodactyly was observed in Pdn/Pdn. In the observation of cell death patterns by means of vital stain, Pdn/+ and +/+ treated with teratogenic dose of 5-FU on day 10 showed extensive necrosis in the preaxial mesoderm of the footplate and subsequently showed similar cell death pat-tern to non-treated Pdn/Pdn. In Pdn/Pdn treated with teratogenic dose of 5-FU on day 10, extensive necrosis in the preaxial mesoderm was marked and disappeared later than that of Pdn/+ or +/+.