Refining risk estimates for lead in drinking water based on the impact of genetics and diet on blood lead levels using the Collaborative Cross mouse population.
Refining risk estimates for lead in drinking water based on the impact of genetics and diet on blood lead levels using the Collaborative Cross mouse population.
复制标题
使用协作交叉小鼠群，根据遗传学和饮食对血铅水平的影响，完善饮用水中铅的风险估计。
DOI：
10.1093/toxsci/kfad054
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Threadgill,DavidW
中科院分区：
文献类型：
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作者：
Cuomo,Danila;Nitcher,Megan;Barba,Estefania;Feinberg,AndrewP;Rusyn,Ivan;Chiu,WeihsuehA;Threadgill,DavidW
血铅水平(BLL)是一种常用的生物标志物，用于评估与健康影响的关系。然而，减少铅的不利影响的干预措施需要将BLL与外部暴露联系起来。此外，风险缓解行动需要确保保护更容易积累铅的易受影响的个人。由于很少有数据可以量化铅的生物动力学个体间的变异性，我们调查了遗传和饮食对遗传多样性协作杂交(CC)小鼠群体血铅水平的影响。来自49个CC品系的成年雌性小鼠分别接受标准小鼠饲料或模拟美国饮食的饲料，同时给予给予1000 ppm铅的沃特德锂盐，持续4 周。在研究的两个方面，都观察到了菌株间的变异性；然而，在美国饮食喂养的动物中，BLL更大且更具变异性。重要的是，美国人饮食中不同品系之间的血淋巴细胞变异程度(2.3)大于设定监管标准时使用的默认变异性估计值(1.6)。遗传分析发现与饮食相关的单倍型与BLL的变异有关，主要由PWK/PhJ菌株造成。这项研究量化了由于遗传背景、饮食和它们之间的相互作用而导致的血铅水平的变化，并观察到它可能比目前饮用水中铅的监管标准假设的要大。此外，这项工作强调有必要确定血铅的个体间差异，以确保适当的公共卫生干预措施，旨在减少铅对人类健康的风险。
Blood lead (Pb) level (BLL) is a commonly used biomarker to evaluate associations with health effects. However, interventions to reduce the adverse effects of Pb require relating BLL to external exposure. Moreover, risk mitigation actions need to ensure protection of more susceptible individuals with a greater tendency to accumulate Pb. Because little data is available to quantify inter-individual variability in biokinetics of Pb, we investigated the influence of genetics and diet on BLL in the genetically diverse Collaborative Cross (CC) mouse population. Adult female mice from 49 CC strains received either a standard mouse chow or a chow mimicking the American diet while being provided waterad libitumwith 1000 ppm Pb for 4 weeks. In both arms of the study, inter-strain variability was observed; however, in American diet-fed animals, the BLL was greater and more variable. Importantly, the degree of variation in BLL among strains on the American diet was greater (2.3) than the default variability estimate (1.6) used in setting the regulatory standards. Genetic analysis identified suggestive diet-associated haplotypes that were associated with variation in BLL, largely contributed by the PWK/PhJ strain. This study quantified the variation in BLL that is due to genetic background, diet, and their interactions, and observed that it may be greater than that assumed for current regulatory standards for Pb in drinking water. Moreover, this work highlights the need of characterizing inter-individual variation in BLL to ensure adequate public health interventions aimed at reducing human health risks from Pb.