In vitro preclinical testing of nonoxynol-9 as potential anti-human immunodeficiency virus microbicide: a retrospective analysis of results from five laboratories
In vitro preclinical testing of nonoxynol-9 as potential anti-human immunodeficiency virus microbicide: a retrospective analysis of results from five laboratories
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DOI：
10.1128/aac.50.2.713-723.2006
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发表时间：
2006-02-01
影响因子：
4.9
通讯作者：
Reichelderfer, P
中科院分区：
文献类型：
--
作者：
Beer, BE;Doncel, GF;Reichelderfer, P
第一个作为杀微生物剂进行临床评估的产品含有非离子表面活性剂nonoxynol-9（壬基苯氧基聚乙氧基乙醇；N-9）。许多实验室已使用 N-9 作为杀菌剂测定的对照化合物。然而，尚未对实验室之间的结果进行公开比较，也没有尝试建立杀微生物剂临床前测试的标准化方案。在这项研究中，我们比较了过去六年中五个不同实验室进行的 127 项 N-9 毒性和 72 项功效测定的结果，并使用 14 种不同的细胞系或组织进行。使用标准偏差测量两倍、三倍和五倍差异的测定内重现性。使用一般线性模型评估测定间重现性，并使用逐步回归研究变量之间的相互作用。相同 N-9 浓度、细胞类型、测定持续时间和实验室内的测定内重现性在标准偏差的两倍水平上保持一致。对于测定间重现性，细胞系、测定持续时间和 N-9 浓度都是变异性的重要来源 (P < 0.01)。对于相似暴露持续时间的测定，N-9 的半最大毒性浓度在实验室之间相似，但这些相似性随着 N-9 测试浓度的降低而降低。细胞长时间（> 24 小时）和短时间（< 2 小时）暴露于 N-9 的结果均显示出差异，而暴露于 N-9 4 至 8 小时的测定结果没有显着差异。这是首次对不同实验室使用不同方案获得的临床前 N-9 毒性水平进行比较的分析。这项比较工作可用于制定标准化的杀菌剂测试方案，这将有助于将潜在的杀菌剂推进临床试验。
The first product to be clinically evaluated as a microbicide contained the nonionic surfactant nonoxynol-9 (nonylphenoxypolyethoxyethanol; N-9). Many laboratories have used N-9 as a control compound for microbicide assays. However, no published comparisons of the results among laboratories or attempts to establish standardized protocols for preclinical testing of microbicides have been performed. In this study, we compared results from 127 N-9 toxicity and 72 efficacy assays that were generated in five different laboratories over the last six years and were performed with 14 different cell lines or tissues. Intra-assay reproducibility was measured at two-, three-, and fivefold differences using standard deviations. Interassay reproducibility was assessed using general linear models, and interaction between variables was studied using step-wise regression. The intra-assay reproducibility within the same N-9 concentration, cell type, assay duration, and laboratory was consistent at the twofold level of standard deviations. For interassay reproducibility, cell line, duration of assay, and N-9 concentration were all significant sources of variability (P < 0.01). Half-maximal toxicity concentrations for N-9 were similar between laboratories for assays of similar exposure durations, but these similarities decreased with lower test concentrations of N-9. Results for both long (> 24 h) and short (< 2 h) exposures of cells to N-9 showed variability, while assays with 4 to 8 h of N-9 exposure gave results that were not significantly different. This is the first analysis to compare preclinical N-9 toxicity levels that were obtained by different laboratories using various protocols. This comparative work can be used to develop standardized microbicide testing protocols that will help advance potential microbicides to clinical trials.