DEVELOPMENT OF BASAL AND INDUCED ARYL-HYDROCARBON (BENZO[A]PYRENE) HYDROXYLASE-ACTIVITY IN THE CHICKEN-EMBRYO INOVO
DEVELOPMENT OF BASAL AND INDUCED ARYL-HYDROCARBON (BENZO[A]PYRENE) HYDROXYLASE-ACTIVITY IN THE CHICKEN-EMBRYO INOVO
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DOI：
10.1073/pnas.80.11.3372
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发表时间：
1983-01-01
期刊：
影响因子：
--
通讯作者：
BLOOM, SE
中科院分区：
文献类型：
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作者：
HAMILTON, JW;DENISON, MS;BLOOM, SE
肝微粒体混合功能氧化酶系统的发展进行了研究，以确定胚胎酶活性的基础水平和整个生长和分化过程中该系统的诱导。从孵育（DI）5天至孵化后10天，从肝脏作为离散器官首次出现开始，测定鸡胚肝脏的基础和诱导型肝芳烃羟化酶（AHHase;在别处称为AHH）活性。在3和4 DI时测定全胚胎和内脏制备物。在所有制剂中，从3 DI至孵化，基础AHHase活性等于或大于成虫水平（约0.3-0.5 nmol/min/mg）。在孵化时，基础活性比成人值增加3倍。鸡胚肝在5至6 DI之间开始诱导，与肝细胞分化同时发生。24小时3，4，3“，4”-四氯联苯诱导的AHHase活性的发育曲线显示，从孵化后7天到10天，诱导量是对照的15-30倍，在孵化后14天和第1天，最大值为15 nmol/min/mg，比活性比成虫的最大诱导量高50%以上。胚胎AHHase活性也由2，3，7，8-四氯二苯并-p-二恶英、3-甲基胆蒽、β-二苯并-p-二恶英、β-二苯并-p-二恶英诱导。萘酮和苯巴比妥钠。整个胚胎发育过程中的诱导动力学与成年鸡和其他动物的报告相似。这些研究结果表明，在非常早期的胚胎发育，然后在肝脏分化的混合功能氧化酶系统的发展。肝脏AHHase活性在整个发育过程和围产期都是可诱导的，但这种活性受到严格的发育调控。鸡胚具有成人水平的AHHase活性，足以在肝细胞分化前后实现前诱变剂/致癌物的代谢活化。
The development of the hepatic microsomal mixed-function oxidase system was studied to determine the basal level of embryonic enzyme activity and the inducibility of this system throughout growth and differentiation. Chicken embryo livers were assayed for basal and inducible hepatic aryl hydrocarbon hydroxylase (AHHase; designated elsewhere as AHH) activity from the first appearance of the liver as a discrete organ at 5 days of incubation (DI) through day 10 after hatching. Whole-embryo and viscera preparations were assayed at 3 and 4 DI. Basal AHHase activity was equal to or greater than adult levels from 3 DI through hatching in all preparations (approximately 0.3-0.5 nmol/min per mg). A 3-fold increase in basal activity above adult values occurred at hatching. The onset of inducibility in chicken embryo liver between 5 and 6 DI was concomitant with hepatocyte differentiation. A developmental profile of 24-h 3,4,3'',4''-tetrachlorobiphenyl-induced AHHase activity showed 15-30-fold induction over controls from 7 DI through day 10 after hatching, with a maximum of 15 nmol/min per mg at 14 DI and day 1 after hatching, a specific activity > 50% greater than maximal induction in the adult. Embryonic AHHase activity was also induced by 2,3,7,8-tetrachlorodienzo-p-dioxin, 3-methylcholanthrene, .beta.-naphthoflavone and sodium phenobarbital. Induction kinetics throughout embryonic development were similar to those reported for the adult chicken and other animals. These findings demonstrate development of a mixed-function oxidase system in very early embryogenesis and then in the liver as it differentiates. Liver AHHase activity is inducible throughout development and perinatally, but such activity is under such strict developmental regulation. The chicken embryo has adult levels of AHHase activity which would be sufficient to achieve metabolic activation of promutagens/carcinogens before and after hepatocyte differentiation.