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Two-cell embryos, obtained from the C57B/ 6N and DBA/2N strains, were cultured in media that supported in vitro differentiation and that contained [3Hjbenzo[a]pyrene.High-pressure liquid chromatography of the activated intermediates formed during in vitro early embryonic development indicated that the onset of polynuclear aromatic hydrocarbon activation coincided with blastocyst formation. Comparison ofindividual oxygenated intermediates metabolically formed from embryos genetically "responsive" or "nonresponsive" to aromatic hydrocarbons revealed significant quantitative differences in the production of dihydrodiol, quinone, and phenolic derivatives. In addition to exhibiting basal mixed-function oxidase activity, blastocysts were also responsive to enzymatic induction when exposed to 2,-3,7,8-tetrachlorodibenzo-p-dioxin. The presence of operative metabolite-detoxifying pathways was also assayed. Enzymatic treatment of water-soluble metabolites with P-glucuronidase or arylsulfatase revealed that neither glucuronic acid conjugates nor sulfate ester derivatives were present. These data, therefore, provide direct evidence that late preimplantation mouse embryos (day 3V ofgestation) are similar to later developmental stages in having the enzymatic capability for xenobiotic activation and enzyme induction but are dissimilar with respect to their detoxification mechanism(s). Moreover, the ability of preimplantation embryos to activate directly polynuclear aromatic hydrocarbon to bioreactive intermediates may be of importance in assessing the ontological susceptibility of the developing embryo to carcinogenic or teratogenic chemicals.The polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) is representative of a class of environmental agents that require biotransformation by the microsomal mixed-function oxidase system (MFO) to produce reactive intermediates (1). In various strains of mice, there is a genetic difference in the inducibility ofaryl hydrocarbon hydroxylase (2) and ofseveral other enzyme components of the MFO system (3). This genetic difference, as observed between C57BL/6N (responsive) and DBA/2N (nonresponsive) mice, has been correlated with a differential susceptibility to BaP-induced developmental effects (4-6).The influence of environmental chemicals on mammalian embryonic development may result in selective embryotoxic effects, in modifying cellular division rates, or in altering the differentiational potential of primordial cell types (reviewed in refs. 7 and 8). The extent of embryonic response in part may be influenced by the mother's or developing embryo's metabolic activities in producing bioreactive species (9). Previous investigations have concentrated on determining metabolic activities in maternal and in middle to late gestational fetal systems (10-12). A recent report on BaP-induced sister chromatid exchange in postimplantation mouse embryos suggests that the activating enzymes in biotransformation pathways may be functioning at gestational day 71i (13).The role of activation and ...

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Physical measurements were made on the cytosolic form of the liver [3H]dexamethasone receptor. These include a Stokes radius of 3.5 nm, determined by gel filtration, and sedimentation coefficients of 5.1 and 7-8S, by sucrose-density-gradient centrifugation. From these measurements, the following physical properties were calculated: apparent mol. wt. 78000 (the 5.1 S form); D app. 6.1 X 10(-7) cm2-S-1; f/fo 1.25; axial ratio 4.7; these indicate a globular protein. Measurements of sedimentation coefficient of cytosol steroid-receptor complexes previously subjected to various activating conditions gave different values and lead to the conclusion that the mechanism of activation in vitro enabling the steroid-receptor complex to bind to DNA is more complex than simple disaggregation to a uniform size.