发表机构
Duke University（杜克大学）
机构由 AI 辅助整理，请以论文原文为准。AI 中文总结
本研究以秀丽隐杆线虫为模型，采用新型检测方法和统计模型，测试铅与苯并[a]芘联合暴露的神经毒性加和性，发现二者在特定剂量组合下存在局部不对称协同作用。
AI 中文摘要
环境污染物暴露是公认的神经毒性诱因，会引发多种神经系统疾病。现实场景中，这种暴露涉及复杂混合物，其组分的联合效应可能与各组分单独效应的预测值不同。表征此类相互作用并依据严谨的加和性概念对其进行测试，是评估神经毒理学风险的核心。针对两种广泛存在且具有独立神经毒性的污染物——铅（Pb）和苯并[a]芘（BaP），本研究采用新型秀丽隐杆线虫（Caenorhabditis elegans）检测方法，让线虫暴露于一系列剂量下的单一及联合处理，对单个多巴胺能神经元水平的形态损伤进行序数尺度量化。为分析这些数据，我们将序数响应的完整分布建模为未暴露和最大受损剖面的凸混合，该混合的权重随化学剂量变化，通过单调样条灵活建模；对于联合效应，则在径向坐标系中建模。我们通过似然比检验对已确立的零模型评估加和性，并通过参数自助法进行校准。将该分析应用于秀丽隐杆线虫检测，结果显示Pb与BaP之间存在局部、不对称的协同作用，集中于中等BaP暴露与高Pb暴露的组合区域。
英文摘要
Exposure to environmental contaminants is a recognized cause of neurotoxicity, contributing to the onset of a broad range of neurological conditions. In realistic settings, such exposure involves com- plex mixtures, and the combined effect of their components may differ from what their individual effects would predict. Characterizing such interactions and testing them against a principled notion of additivity is central to assessing the neurotoxicological risk. We take up these questions for two widespread and independently neurotoxic pollutants, lead (Pb) and benzo[a]pyrene (BaP), through a novel C. elegans assay in which nematodes were subjected to single and joint exposures across a range of doses. Morphological damage is quantified on an ordinal scale at the level of individual dopaminergic neurons. To analyze these data, we model the full distribution of the ordinal response as a convex mixture between an unexposed and a maximally affected profile. The weight of this mixture varies with chemical doses, modeled flexibly via monotone splines and, for the joint effect, in a radial coordinate system. Additivity is assessed via a likelihood ratio test against established null models, and is calibrated via parametric bootstrap. Applied to the C. elegans assay, our analysis reveals a localized, asymmetric synergy between Pb and BaP, concentrated where moderate BaP meets high Pb exposure.
