Ontogenetic expression of polycyclic aromatic compound-inducible monooxygenase activities and forms of cytochrome P-450 in rabbit. Evidence for temporal control and organ specificity of two genetic regulatory systems.
Ontogenetic expression of polycyclic aromatic compound-inducible monooxygenase activities and forms of cytochrome P-450 in rabbit. Evidence for temporal control and organ specificity of two genetic regulatory systems.
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多环芳香族化合物诱导的单加氧酶活性和细胞色素 P-450 形式在兔体内的个体发育表达。
DOI：
10.1016/s0021-9258(17)40218-3
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发表时间：
1977
期刊：
影响因子：
--
通讯作者：
D. Nebert
中科院分区：
文献类型：
--
作者：
S. Atlas;A. Boobis;J. Felton;S. Thorgeirsson;D. Nebert
测定了对照组和3-甲基胆蒽处理的新西兰白色兔从出生前5天到成年（110天）肝微粒体细胞色素P-450总含量和5种单加氧酶活性的发育曲线。同时通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析微粒体。3-甲基胆蒽诱导的N-乙酰芳基胺（2-乙酰氨基芴）N-羟化酶在54，000道尔顿的电泳带中的增加与还原血红素蛋白CO复合物的Soret峰中约2nm的光谱蓝移相当接近，并且诱导的N-羟化酶活性被3-甲基胆蒽显著抑制。第阿尔法.. -萘酮体外;这些参数在10日龄及以上的家兔中产生。3-甲基胆蒽诱导的联苯4-羟化酶在前10天的胎儿和新生儿中至少是2倍，在16 - 40天的年龄之间不到2倍，在50天及以上的兔子中不存在。细胞色素P-450介导的单加氧酶与某些致癌物和其他环境污染物的代谢增强有关。这些数据提供了至少三种不同的组织特异性形式的诱导型单加氧酶活性及其相关的P-450亚基的组织特异性基因的调节和修改这些时间基因的证据。这两种类型的遗传控制可能在对化学致癌作用或毒性的易感性中发挥作用，作为年龄或组织定位的函数。
Developmental curves of liver microsomal cytochrome P-450 total content and five monooxygenase activities from control and 3-methylcholanthrene-treated New Zealand White rabbits were determined from 5 days prior to birth to adulthood (110 days of age). Microsomes were concomitantly analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. N-Acetylarylamine (2-acetylaminofluorene) N-hydroxylase induction by 3-methylcholanthrene parallels quite closely increases in an electrophoretic band of 54,000 daltons and the approximately 2 nm spectral shift to the blue in the Soret peak of the reduced hemoprotein CO complex, and the induced N-hydroxylase activity is markedly inhibited by ..cap alpha..-naphthoflavone in vitro; these parameters develop in rabbits of age 10 days and older. Biphenyl 4-hydroxylase induction by 3-methylcholanthrene is at least 2-fold in the fetus and neonate for the first 10 days of age, is less than 2-fold between 16 and 40 days of age, and is absent in rabbits 50 days and older. Cytochrome P-450-mediated monooxygenases are implicated in the metabolic potentiation of certain carcinogens and other environmental pollutants. These data provide evidence for at least three different tissue-specific forms of regulation of inducible monooxygenase activities and their associated P-450 subunits by tissue-specific genes and the modification of these by temporal genes. These two types of genetic control may play a role in the susceptibility to chemical carcinogenesis or toxicity as a function of either age or tissue localization.