Kleinstreuer Nicole C, Ceger Patricia C, Allen David G, Strickland Judy, Chang Xiaoqing, Hamm Jonathan T, Casey Warren M
Integrated Laboratory Systems, in support of the National Toxicology Program Interagency Center for Evaluation of Alternative Toxicological Methods (NICEATM), Research Triangle Park, North Carolina, USA.
Environ Health Perspect. 2016 May;124(5):556-62. doi: 10.1289/ehp.1510183. Epub 2015 Oct 2.
Novel in vitro methods are being developed to identify chemicals that may interfere with estrogen receptor (ER) signaling, but the results are difficult to put into biological context because of reliance on reference chemicals established using results from other in vitro assays and because of the lack of high-quality in vivo reference data. The Organisation for Economic Co-operation and Development (OECD)-validated rodent uterotrophic bioassay is considered the "gold standard" for identifying potential ER agonists.
We performed a comprehensive literature review to identify and evaluate data from uterotrophic studies and to analyze study variability.
We reviewed 670 articles with results from 2,615 uterotrophic bioassays using 235 unique chemicals. Study descriptors, such as species/strain, route of administration, dosing regimen, lowest effect level, and test outcome, were captured in a database of uterotrophic results. Studies were assessed for adherence to six criteria that were based on uterotrophic regulatory test guidelines. Studies meeting all six criteria (458 bioassays on 118 unique chemicals) were considered guideline-like (GL) and were subsequently analyzed.
The immature rat model was used for 76% of the GL studies. Active outcomes were more prevalent across rat models (74% active) than across mouse models (36% active). Of the 70 chemicals with at least two GL studies, 18 (26%) had discordant outcomes and were classified as both active and inactive. Many discordant results were attributable to differences in study design (e.g., injection vs. oral dosing).
This uterotrophic database provides a valuable resource for understanding in vivo outcome variability and for evaluating the performance of in vitro assays that measure estrogenic activity.
Kleinstreuer NC, Ceger PC, Allen DG, Strickland J, Chang X, Hamm JT, Casey WM. 2016. A curated database of rodent uterotrophic bioactivity. Environ Health Perspect 124:556-562; http://dx.doi.org/10.1289/ehp.1510183.
新型体外方法正在被开发用于识别可能干扰雌激素受体（ER）信号传导的化学物质，但由于依赖基于其他体外试验结果建立的参考化学物质，且缺乏高质量的体内参考数据，其结果难以放入生物学背景中。经济合作与发展组织（OECD）验证的啮齿动物子宫增重生物测定法被认为是识别潜在ER激动剂的“金标准”。
我们进行了一项全面的文献综述，以识别和评估子宫增重研究的数据，并分析研究变异性。
我们回顾了670篇文章，这些文章包含使用235种独特化学物质进行的2615次子宫增重生物测定的结果。研究描述符，如物种/品系、给药途径、给药方案、最低效应水平和测试结果，被记录在子宫增重结果数据库中。根据子宫增重监管测试指南的六项标准评估研究。符合所有六项标准的研究（对118种独特化学物质进行的458次生物测定）被视为类似指南（GL），随后进行分析。
76%的GL研究使用了未成熟大鼠模型。与小鼠模型（36%呈阳性结果）相比，大鼠模型中阳性结果更为普遍（74%呈阳性结果）。在至少有两项GL研究的70种化学物质中，18种（占26%）结果不一致，被归类为既有活性又无活性。许多不一致的结果归因于研究设计的差异（例如，注射与口服给药）。
这个子宫增重数据库为理解体内结果变异性和评估测量雌激素活性的体外试验性能提供了宝贵资源。
Kleinstreuer NC, Ceger PC, Allen DG, Strickland J, Chang X, Hamm JT, Casey WM. 2016. A curated database of rodent uterotrophic bioactivity. Environ Health Perspect 124:556 - 562; http://dx.doi.org/
Zotero 插件
