Interaction of dietary zinc, genetic strain, and acetazolamide in teratogenesis in mice.
The effect of dietary zinc and genetic strain on acetazolamide-induced malformations was assessed. CBA (sensitive) and SWV (resistant) mice were fed purified diets containing five different levels of zinc throughout gestation and were given acetazolamide orally for a limited period during organogenesis. Controls received either no treatment or the drug vehicle. Litters were assessed for resorptions and malformations at term. The significance for influencing litter outcome was tested for the three main treatments: strain, dietary zinc level, and acetazolamide dose, plus their interactions. The magnitude of the litter response was strongly influenced by strain. The incidence of forelimb ectrodactyly, a characteristic malformation caused by acetazolamide, was much greater in CBA than in SWV fetuses. SWV fetuses had no ectrodactyly when dams were fed at least 9 micrograms/g zinc, but 5-8% showed ectrodactyly when dams received a zinc-deficient (0.4 or 4.5 micrograms/g) diet. The incidence of ectrodactyly in the CBA strain decreased as dietary zinc increased, but was still present when dams were fed a high (1,000 micrograms/g) zinc diet. The incidence of resorptions and total abnormal sites from litters of dams receiving acetazolamide decreased as dietary zinc increased, with the magnitude of the response being influenced by the strain. A significant (dietary zinc X acetazolamide) and (strain X acetazolamide) interaction was found for the ectrodactyly response. The results demonstrate the importance of considering interactions among genetic strain, diet, and drugs, as well as single factors as determinants of fetal risk.
D000014:Abnormalities, Drug-Induced / Q000196:embryology*; D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D004032:Diet; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D051379:Mice; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains / Q000235:genetics*; D011247:Pregnancy; D013223:Statistics as Topic; D015032:Zinc / Q000008:administration & dosage* / Q000494:pharmacology
D015032:Zinc; D000086:Acetazolamide