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诱变剂致突变性剂量反应关系中的兴奋效应证据。

Evidence for hormesis in mutagenicity dose-response relationships.

机构信息

Department of Public Health, University of Massachusetts, Amherst, MA 01003, USA.

出版信息

Mutat Res. 2011 Dec 24;726(2):91-7. doi: 10.1016/j.mrgentox.2011.04.006. Epub 2011 Apr 21.

DOI:10.1016/j.mrgentox.2011.04.006
PMID:21540124
Abstract

This study assessed the occurrence of hormetic dose responses from three previously published data sets [1-3] with 825 chemicals in three Ames assay tester strains (i.e., TA97, TA98, TA100) with and without the S9 fraction, using a five dose protocol and semi-log dose spacing. Ninety-five (95) (11.5%) chemicals satisfied the multiple a priori entry criteria, with a total of 107 assays. Of the assays satisfying the entry criteria, 61 involved TA100, a strain that detects base-pair substitution mutations. 29.5% (18/61) satisfied the statistical evaluative criteria for hormesis, exceeding that predicted by chance by 4.0-fold (p<0.001). The remaining 46 assays involved TA97 and TA98, strains that detect frameshift mutations. Of these 46 assays, the overall responses for the lowest two doses closely approximated the control response (e.g., 101.77% of the control for TA98; 99.20% for TA97). Only 2.2% (1/46) of the assays satisfied the evaluative criteria for hormesis. In conclusion, these data support a hormetic model for TA100, whereas the responses for TA97 and TA98 are consistent with a threshold dose-response model.

摘要

本研究评估了三个先前发表的数据集中[1-3]中 825 种化学物质在三个 Ames 试验测试菌株(TA97、TA98、TA100)中存在和不存在 S9 组分时的兴奋剂量反应发生情况,使用了五剂量方案和半对数剂量间距。95(95)(11.5%)种化学物质符合多个事先设定的进入标准,总共有 107 个试验。在符合进入标准的试验中,61 个涉及 TA100,该菌株可检测碱基对替换突变。满足兴奋统计评估标准的试验占 61%,比随机预测高出 4.0 倍(p<0.001)。其余 46 个试验涉及 TA97 和 TA98,这两种菌株可检测移码突变。在这 46 个试验中,最低两个剂量的总体反应非常接近对照反应(例如,TA98 的对照反应为 101.77%;TA97 的对照反应为 99.20%)。只有 2.2%(1/46)的试验符合兴奋的评估标准。总之,这些数据支持 TA100 的兴奋模型,而 TA97 和 TA98 的反应与阈值剂量反应模型一致。

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