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用于矿物油遗传毒性测试的改良细菌诱变性试验评估

Evaluation of modified bacterial mutagenicity assays for the genotoxicity testing of mineral oils.

作者信息

Brooks T M, Priston R A, Wright A S, Watson W P

机构信息

Shell Research Ltd, Sittingbourne Research Centre, Sittingbourne, Kent, UK.

出版信息

Mutagenesis. 1995 Sep;10(5):409-15. doi: 10.1093/mutage/10.5.409.

Abstract

A modified bacterial mutagenicity assay based on the Ames Salmonella/mammalian microsome test has been developed for application in the genotoxicity testing of mineral oils. The assay uses washed microsomes from rat liver in place of S9 fraction in order to increase the sensitivity of detection of genotoxicity. The modified assay was used to test a series of oils for which skin carcinogenicity bioassay data in mice were available. Oils were tested as emulsions in water using Tween 80 as a dispersant. A mutagenicity index for each oil was obtained using non-linear regression analysis of data from the dose-response curve. The results showed an empirical correlation between increasing mutagenicity index, carcinogenicity and the polycyclic aromatic hydrocarbon content of the oils. The washed-microsome assay was also compared with modified Ames assays developed by Blackburn et al. (Cell Biol. Toxicol., 1, 40, 1984; Cell Biol. Toxicol., 2, 63, 1986) which employed increased levels of S9 (rat and hamster liver) to test dimethyl sulphoxide extracts of oils. The washed-microsome assay can be used for the testing of whole oils rather than extracts which are necessary for the modified Ames assay. It is recognised that the determinants of carcinogenic activity in vivo include promoting activity which such assays are unable to detect. Nevertheless, such modified bacterial assays may be a useful prescreen since genotoxicity is recognised as a key initial step in carcinogenesis.

摘要

一种基于艾姆斯沙门氏菌/哺乳动物微粒体试验的改良细菌致突变性试验已被开发出来,用于矿物油的遗传毒性测试。该试验使用大鼠肝脏的洗涤微粒体代替S9组分,以提高遗传毒性检测的灵敏度。改良后的试验用于测试一系列有小鼠皮肤致癌性生物测定数据的油。油以水包乳液的形式使用吐温80作为分散剂进行测试。通过对剂量反应曲线数据进行非线性回归分析,得到每种油的致突变性指数。结果表明,致突变性指数增加、致癌性与油中的多环芳烃含量之间存在经验相关性。还将洗涤微粒体试验与Blackburn等人开发的改良艾姆斯试验(《细胞生物学与毒理学》,1,40,1984;《细胞生物学与毒理学》,2,63,1986)进行了比较,后者采用增加S9(大鼠和仓鼠肝脏)水平来测试油的二甲基亚砜提取物。洗涤微粒体试验可用于测试全油,而不是改良艾姆斯试验所需的提取物。人们认识到,体内致癌活性的决定因素包括此类试验无法检测到的促进活性。然而,由于遗传毒性被认为是致癌作用的关键起始步骤,此类改良细菌试验可能是一种有用的预筛选方法。

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