Localization of radioactivity from 2-methoxy[1,2-14C]ethanol in maternal and conceptus compartments of CD-1 mice

Abstract

2-Methoxyethanol (ME) induces paw malformations in CD-1 mice when given by gavage on gestation day (gd) 11 (vaginal plug + day = gd 0). The distribution of radioactivity originating from 2-methoxy[1,2-14C]ethanol ([14C]ME) was examined by liquid scintillation spectrophotometry and whole body autoradiography in pregnant (gd 11) CD-1 mice from 5 min to 48 hr after oral administration. Each dam received either a trace dose of [14C]ME (0.92 mumol; 13 muCi) combined with an unlabeled teratogenic dose (187 mumol). By 5 min after the trace dose was administered, 14C had distributed throughout the maternal and conceptus compartments. Radioactivity in the maternal compartment was most concentrated in the liver, blood and gastrointestinal tract. Conceptus 14C was associated with the placenta, yolk sac, and embryonal structures such as limb buds, somites, and neuroepithelium. The concentration of blood 14C plateaued within 30 min after administration of the trace or combined trace/teratogenic dose. It remained stable for 1.5 hr and then gradually declined, reaching 2 to 10% of the maximal concentration by 48 hr. 14C content in the maternal liver, conceptuses, and embryos per se was always greater than that of the blood and was inversely related to ME dose at 6 hr but not 48 hr. At 6 hr after administration of the trace dose, 69% of total liver and 33% of embryonal 14C were acid insoluble. Tissue-specific interaction with [14C]ME was demonstrated by the distribution of acid insoluble radioactivity among various cellular components of the maternal liver and embryo. The findings indicate that the embryo is readily susceptible to blood borne ME and/or its metabolites. In addition, the chemical characteristics of the labeled molecule(s) apparently favored label incorporation into macromolecules by the liver and embryo.