SULFOTRANSFERASE-MEDIATED DNA-BINDING OF N-HYDROXYARYLAMINES(AMIDE) IN LIVER CYTOSOLS FROM HUMAN AND EXPERIMENTAL-ANIMALS
SULFOTRANSFERASE-MEDIATED DNA-BINDING OF N-HYDROXYARYLAMINES(AMIDE) IN LIVER CYTOSOLS FROM HUMAN AND EXPERIMENTAL-ANIMALS
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DOI：
10.1093/carcin/13.8.1307
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发表时间：
1992-08-01
期刊：
影响因子：
4.7
通讯作者：
KATO, R
中科院分区：
文献类型：
--
作者：
ABUZEID, M;YAMAZOE, Y;KATO, R
研究了细胞溶质磺基转移酶介导的致癌性N-羟基芳基胺（酰胺）结合的特性，并在体外实验动物和人类中进行了比较。人细胞液对2-羟基氨基-6-甲基双吡啶并[1，2-a：3 '，2'-d]咪唑（N-hydroxy-Glu-P1）、N-羟基-2-氨基芴（N-hydroxy-2-aminonuorene，N-hydroxy-AF）和N-羟基-2-乙酰氨基芴（N-hydroxy-AAF）具有显著的硫酸化活性，但对2-羟基氨基-3-甲基咪唑并[4，5-f]喹啉（N-hydroxy-IQ）没有检测到活性。虽然这些N-羟基芳胺（酰胺）的共价结合的程度在个体之间差异显着，明确的相关性之间观察到的N-羟基芳胺（酰胺）的硫酸化，也与对硝基苯酚硫酸化。小鼠、大鼠、豚鼠、仓鼠、兔、狗和猴的肝细胞液也介导N-羟基-Glu-P-1、N-羟基-AF和N-羟基-AAF的结合，而只有大鼠细胞液显示可检测到N-羟基-IQ的DNA结合。在所检查的物种中，大鼠显示出最高的激活这些N-羟基芳胺（酰胺）的能力。除N-羟基-IQ外，在大鼠、犬和猴中检测到所有检查底物的显著性别相关差异。在动物种属中观察到N-羟基芳基胺（酰胺）之间存在明显相关性，但与对硝基苯酚之间不存在相关性。利用离子交换色谱系统，对硝基苯酚在人肝中的硫酸化活性被分成两个部分，并且N-hydroxy-AF的PAPS依赖的DNA结合主要由后一部分支持。在蛋白质印迹，免疫反应性蛋白质检测在这些馏分中使用针对大鼠肝N-羟基-AAF磺基转移酶的抗体。在人肝细胞质中也检测到该条带，其量存在相当大的个体差异。这些结果表明，在人类以及实验动物物种中，一种密切相关的磺基转移酶形式参与了PAPS介导的N-羟基芳基胺（酰胺）的活化。
Characteristics of cytosolic sulfotransferase-mediated binding of carcinogenic N-hydroxyarylamines(amide) have been investigated and compared among experimental animal species and humans in vitro. Human cytosols exhibited significant sulfating activities towards 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-hydroxy-Glu-P1), N-hydroxy-2-aminonuorene (N-hydroxy-AF) and N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF), but had no detectable activity toward 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). Although the extent of the covalent binding of these N-hydroxyarylamines(amide) differed significantly among individuals, clear correlations were observed among the sulfation of N-hydroxyarylamines (amide) and also with p-nitrophenol sulfation. Hepatic cytosols from mouse, rat, guinea-pig, hamster, rabbit, dog and monkey also mediated the binding of N-hydroxy-Glu-P-1, N-hydroxy-AF and N-hydroxy-AAF, while only rat cytosols showed detectable DNA binding of N-hydroxy-IQ. Among the species examined, rat showed the highest capability for activating these N-hydroxyarylamines(amides). Significant sex-related differences were detected in rat, dog and monkey for all substrates examined, except N-hydroxy-IQ. Clear correlations were observed in the animal species between N-hydroxyarylamines(amide), but not with p-nitrophenol. Using an ion-exchange chromatographic system, sulfating activity of p-nitrophenol in human livers was separated into two fractions and the PAPS-dependent DNA binding of N-hydroxy-AF was supported mainly by the later fraction. On Western blots, an immunoreactive protein was detected in these fractions using an antibody raised against rat hepatic N-hydroxy-AAF sulfotransferase. The band was also detected in human hepatic cytosols with considerable individual variation in their amounts. These results indicate the involvement of a closely related form(s) of sulfotransferase in the PAPS-mediated activation of N-hydroxyarylamines(amide) in human as well as in the experimental animal species.