Effect of actinomycin D and urethan on successive litters and generations of mice

Sequential litters and generations of A/He mice were given repeated injections of actinomycin D or urethan to study effects on fertility, embryotoxicity, teratogenicity, and carcinogenicity. The drugs were given every other day throughout pregnancy. Seven weeks separated each mating and course of treatment. Both drugs had a deleterious effect on fetal development dependent on dosage and litter series. The largest dosages blocked development completely; the effect of 50 μg/kg actinomycin D lasted through the second mating period. The number of offspring relative to controls was also decreased with smaller dosages. Drug toxicity increased with successive matings. In three consecutive generations commencing with females obtained from the lowest treatment regimen a response was observed similar to that seen in offspring obtained by repeated treatment of the same females. Actinomycin D was less carcinogenic than urethan; an increase in the number of lung tumors was found only in the females used for breeding. Compared to the control group, both breeders and offspring exposed transplacentally had an increased incidence of tumors following urethan administration. Malformations occurred only after urethan treatment.