The effects of 5-fluorouracil and 5-fluorodeoxyuridine used alone and in combination with normal nucleic acid precursors on development of mice in lines selected for low and high expression of Strong's luxoid gene.

Abstract

Pregnant female mice selected for plus- and minus-modifying genes of the limb-skeleton effects of Strong's luxoid gene (1st) were injected ip on day 10 of gestation with 10 or 20 mg/kg 5-fluorouracil (5-FU) or 5-fluorodeoxyuridine (5-FUdR). The incidence and degree of expression of the effects (polydactyly, ectrodactyly, radial hemimelia, tibial hemimelia, pelvic girdle shifts, deformed caudal vertebrae) varied according to the teratogen and dose level. The addition of an equimolecular amount of thymidine, thymine, or uracil greatly potentiated the effects of 20 mg/kg 5-FU, usually resulting in death of the embryos. The addition of an equimolecular amount of thymidine but not of the embryos. The addition of an equimolecular amount of thymidine but not of thymine or uracil partly protected against the effects of 5-FUdR. Both teratogens increased the expression of ist on the limb skeleton. The interactions of the teratogens with the major gene were inhibited by minus- and promoted by plus-modifying genes of 1st. The effects of the teratogenic treatments may be mediated by cell death.