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物种特异性会影响用于仓鼠胚胎细胞转化系统的S9制剂的选择。

Species specificity affects the choice of S9 preparations for use in the hamster embryo cell transformation system.

作者信息

Poiley J A, Raineri R

出版信息

In Vitro. 1984 Aug;20(8):602-6. doi: 10.1007/BF02619608.

Abstract

Before their use as a source of carcinogen-activating enzymes in the hamster embryo cell transformation assay, liver, kidney, lung, and small intestine S9 fractions from Syrian golden hamsters and Sprague-Dawley rats were evaluated for toxicity to hamster embryo target cells. Sprague-Dawley rat liver and kidney S9 were highly toxic to the hamster embryo cells (90 to 100%). When retested at lower concentrations these tissue fractions were still quite toxic (up to 75%). In contrast, hamster liver and kidney S9 were considerably less toxic (14 to 25%). The S9 preparations were also evaluated for their ability to metabolize N-2-acetylaminofluorene to 2-aminofluorene and N-hydroxy-acetylaminofluorene, products that transform hamster embryo cells. Large amounts of N-hydroxy-acetylaminofluorene were formed in the presence of preparations from hamster liver and small intestine, whereas kidney and lung S9 fractions were considerably less active. No detectable levels of N-hydroxy-acetylaminofluorene were formed after incubation of N-2-acetylaminofluorene with any of the rat S9 preparations. High levels of deacetylase activity were found in hamster liver and small intestine S9 fractions, at least eightfold higher than those obtained from equivalent rat preparations. Hamster kidney and lung S9 fractions showed low levels of deacetylase activity. There was no detectable activity in equivalent preparations from rats. When tested with N-2-acetylaminofluorene in the hamster embryo cell clonal transformation system, transformed colonies were obtained with hamster liver S9, with and without an external NADPH-generating system.

摘要

在将叙利亚金黄地鼠和斯普拉格-道利大鼠的肝脏、肾脏、肺和小肠S9组分用作仓鼠胚胎细胞转化试验中致癌物激活酶的来源之前,先评估了它们对仓鼠胚胎靶细胞的毒性。斯普拉格-道利大鼠的肝脏和肾脏S9对仓鼠胚胎细胞具有高毒性(90%至100%)。当在较低浓度下重新测试时,这些组织组分仍然具有相当高的毒性(高达75%)。相比之下,仓鼠的肝脏和肾脏S9毒性要小得多(14%至25%)。还评估了S9制剂将N-2-乙酰氨基芴代谢为2-氨基芴和N-羟基-乙酰氨基芴的能力,这些产物可转化仓鼠胚胎细胞。在存在仓鼠肝脏和小肠的制剂时会形成大量的N-羟基-乙酰氨基芴,而肾脏和肺的S9组分活性则要低得多。用任何大鼠S9制剂孵育N-2-乙酰氨基芴后,均未检测到N-羟基-乙酰氨基芴的形成。在仓鼠肝脏和小肠S9组分中发现了高水平的脱乙酰酶活性,至少比从同等大鼠制剂中获得的活性高八倍。仓鼠肾脏和肺的S9组分显示出低水平的脱乙酰酶活性。在大鼠的同等制剂中未检测到活性。在仓鼠胚胎细胞克隆转化系统中用N-2-乙酰氨基芴进行测试时,无论有无外部NADPH生成系统,仓鼠肝脏S9都能获得转化菌落。

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