The response of mouse embryos to different concentrations of cadmium or mercury with or without low LET radiation was measured in terms of gross morphological anomalies and cellular changes. Single doses of the heavy metals (2 mg/kg body weight) were injected i.p. on day 8 of gestation 30 min before whole-body irradiation. Combined exposures to CdCl2 and X-rays led to a significant reduction in the rate of exencephaly compared with the high frequency after cadmium alone. The hypothesis that metallothionein, a sulphur-rich and metal-binding protein, may be responsible for the antagonism observed could not be confirmed. Mercuric chloride alone induced a low rate of exencephaly and the data on combined treatment suggest additivity with 0.5 and 1.0 Gy X-rays. Regarding cellular criteria, cell death in the eye anlage on day 9 of gestation was significantly suppressed after 0.5 Gy and especially after CdCl2 plus 0.5 Gy compared to cadmium alone. It is assumed that the reduction of cell lethality is correlated with the low occurrence of exencephaly. Concerning the proliferation of neuroblasts, cadmium stimulated the mitotic activity whereas X-rays depressed the proliferation capacity. After the combined treatment a distinct antimitotic effect was established.

Mouse embryos on day 9 of gestation were exposed in utero to 90 rad X-rays. At different time intervals after treatment the eye primordia were examined for cell death. The irradiation caused an altered necrosis pattern compared with day 8, and massive cell killing during a limited time period. The rapid recovery from the pronounced damage points to a high restitution efficiency of the involved tissue.

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.

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