DEVELOPMENTAL ONSET OF MIXED-FUNCTION OXIDASE ACTIVITY IN PRE-IMPLANTATION MOUSE EMBRYOS
DEVELOPMENTAL ONSET OF MIXED-FUNCTION OXIDASE ACTIVITY IN PRE-IMPLANTATION MOUSE EMBRYOS
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DOI：
10.1073/pnas.78.11.6991
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发表时间：
1981-01-01
期刊：
影响因子：
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通讯作者：
LEW, KJ
中科院分区：
文献类型：
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作者：
FILLER, R;LEW, KJ
从C57 BL/6 N和DBA/2N品系获得的双细胞胚胎在支持体外分化和结合[3 H]苯并[a]芘的培养基中培养。高压液相色谱法在体外早期胚胎发育过程中形成的活化中间体表明，多核芳烃活化的发病与胚泡形成相吻合。个体含氧中间体代谢形成的胚胎遗传反应或不响应芳烃的比较显示显着的定量差异的生产二氢二醇，醌和酚类衍生物。除了表现出基础的多功能氧化酶活性，囊胚也响应酶诱导时，暴露于2，3，7，8-四氯二苯并-p-二恶英。还测定了有效代谢物解毒途径的存在。用β-葡聚糖酶处理水溶性代谢物葡萄糖醛酸酶或芳基硫酸酯酶的结果显示，既不存在葡萄糖醛酸缀合物，也不存在硫酸酯衍生物。晚期植入前小鼠胚胎（妊娠3 1/2天）在具有异生物质激活和酶诱导的酶促能力方面与后期发育阶段相似，但在解毒机制方面不同。植入前胚胎直接激活多核芳烃的生物活性中间体的能力可能是重要的，在评估发育中的胚胎的致癌或致畸化学品的本体敏感性。
Two-cell embryos, obtained from the C57BL/6N and DBA/2N strains, were cultured in media that supported in vitro differentiation and that combined [3H]benzo[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 of individual 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 .beta.-glucuronidase or arylsulfatase revealed that neither glucuronic acid conjugates nor sulfate ester derivatives were present. The late preimplantation mouse embryos (day 3 1/2 of gestation) 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). 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.