Combined use of a water-insoluble chemical delivery system and a metabolic activation system in whole embryo culture.
An integrated water-insoluble chemical delivery/metabolic activation/rat embryo culture system is described. Increasing concentrations of diallate dissolved in corn oil caused dose-related embryonic growth retardation in vitro. The presence of a metabolic activating system did not potentiate the effects of diallate in corn oil. The rat hepatic microsomal monooxygenase system was enzymatically active in the presence of a high concentration of corn oil in the rat serum incubation media. Thus, the failure of the metabolic activation system to potentiate the toxicity of diallate in corn oil is not due to an enzymatic deficiency of the hepatic metabolic activation system. As high concentrations of some organic solvents are known to act directly as embryonic poisons in vitro, rat embryos were cultured in incubation media that contained chloroform (0.5 or 2.5%) dissolved in corn oil. This treatment was found to be severely toxic to embryonic growth and differentiation in vitro. Thus, unlike diallate, the embryonic toxicity of chloroform was fully evident when dissolved in the solvent corn oil. Diallate dissolved in acetone retarded embryo growth and caused dysmorphogenesis. When a metabolic activation system and either corn oil or acetone were used together, the incidence of embryolethality and abnormalities were so high that compound treatment effects were difficult to evaluate.
D000014:Abnormalities, Drug-Induced; D000818:Animals; D001711:Biotransformation; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000032:analysis; D009924:Organ Culture Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D013859:Thiocarbamates / Q000378:metabolism / Q000633:toxicity
D013859:Thiocarbamates; D009249:NADP; C004755:di-allate; D004247:DNA