Synergistic Interaction between Vindesine and X-rays in the Prenatal Development of Mice

Abstract

The modification of radiation damage by various concentrations of the oncolytic drug vindesine was studied macroscopically, using mouse embryos during the early organogenesis (days eight and nine of gestation) as the test system. The analysis at term showed that the developmental toxicity of vindesine depends on the dosage and the time of administration. In the lower dose-range (0.25 and 0.35 mg/kg), the only reaction was growth retardation, whereas higher concentrations (0.5 and 1.0 mg/kg) led mainly to an early resorption of implants. The more differentiated stage (day nine) exhibited a much higher sensitivity to vindesine than the embryo on day eight. Conversely, the harmful action of 0.9 Gy X-rays was restricted to the earlier period of organogenesis. The incidence of abnormalities after irradiation on day eight was 4.5 times higher than the one following exposure on day nine. The combined exposures showed a radiosensitizing capacity of the drug with respect to the teratogenic response on day eight only. The pretreatment with 0.25 mg/kg vindesine potentiated the radiation-induced malformation rate by a factor of 1.7, and the one with 0.35 mg/kg vindesine by a factor of 2.4.