物种特异性影响了仓鼠胚胎细胞转化系统中S9制剂的选择。

In Vitro Pub Date : 1984-08-01 DOI:10.1007/BF02619608
J A Poiley, R Raineri
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引用次数: 0

摘要

在将叙利亚金仓鼠和Sprague-Dawley大鼠的肝脏、肾脏、肺和小肠S9部分用作仓鼠胚胎细胞转化试验中致癌激活酶的来源之前,对其对仓鼠胚胎靶细胞的毒性进行了评估。Sprague-Dawley大鼠肝脏和肾脏S9对仓鼠胚胎细胞有高毒性(90% ~ 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大的毒性(高达75%)。相比之下,仓鼠肝脏和肾脏S9的毒性要小得多(14%至25%)。我们还评估了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,这些产物转化为仓鼠胚胎细胞。大量的n -羟基乙酰氨基芴在仓鼠肝脏和小肠的制剂中形成,而肾和肺S9组分的活性要低得多。n -2-乙酰氨基芴与任何大鼠S9制剂孵育后均未形成可检测水平的n -羟基乙酰氨基芴。在仓鼠肝脏和小肠S9组分中发现了高水平的去乙酰化酶活性,比同等大鼠制剂中获得的活性至少高8倍。仓鼠肾和肺S9部分显示低水平的去乙酰化酶活性。在大鼠的等效制剂中没有检测到活性。用n -2-乙酰氨基芴在仓鼠胚胎细胞克隆转化系统中进行实验,在有和没有外部nadph生成系统的情况下,用仓鼠肝脏S9获得转化菌落。
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Species specificity affects the choice of S9 preparations for use in the hamster embryo cell transformation system.

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.

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