Identifying And Evaluating Sources Of Variability In Rodent Studies

识别和评估啮齿动物研究中变异的来源

基本信息

批准号：
8336547
负责人：
grace e kissling
金额：
$ 8.37万
依托单位：
NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8336547
关键词：
Affect Asthma Beds Biological Carcinogens Data Data Quality Databases Development Diagnostic Diet Endotoxins Ensure Estrogens Exposure to Future Genetic Variation Goals Guidelines Infection Ionizing radiation Kidney Kidney Neoplasms Laboratories Laboratory Study Lesion Location Masks Measurement Methodology Methods Molds Mouse Strains National Institute of Environmental Health Sciences Phytoestrogens Predisposition Radiation Rattus Reproduction Research Design Rodent Route Source Testing Time Work drinking water early onset follow-up programs quality assurance research study response tumor

Affect Asthma Beds Biological Carcinogens Data Data Quality Databases Development Diagnostic Diet Endotoxins Ensure Estrogens Exposure to Future Genetic Variation Goals Guidelines Infection Ionizing radiation Kidney Kidney Neoplasms Laboratories Laboratory Study Lesion Location Masks Measurement Methodology Methods Molds Mouse Strains National Institute of Environmental Health Sciences Phytoestrogens Predisposition Radiation Rattus Reproduction Research Design Rodent Route Source Testing Time Work drinking water early onset follow-up programs quality assurance research study response tumor

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项目摘要

Rodent bedding, diet, and drinking water may contain compounds that affect the same endpoints that are the target of NTP's testing program, such as reproduction and development. For example, endotoxins (a byproduct of mold) can mask responses to exposure to asthma-causing agents. Likewise, phytoestrogens in the rodent diet can mask responses to exposure to estrogenic compounds. We are working with the NIEHS Quality Assurance Laboratory to quantify these effects and develop guidelines for limits on contaminants in bedding, diet and drinking water of rodent studies. We contributed to the study design of a multi-strain mouse study in which different strains are exposed to ionizing radiation then followed up for development of tumors. These strains were selected to represent a broad range of genetic variation. Although the data are not yet complete, the early indications are that different strains have a range of susceptibility to radiation and show varying locations and rates of tumors. Some compounds cause kidney tumors in rats exposed for two years. Two-year studies, however, are expensive and time-consuming. We have identified early onset kidney lesions that may predict later kidney tumors in rats. By evaluating data from a number of previous NTP studies, we confirmed the association between early onset lesions and kidney tumors, and showed that the association is not affected by type of diet or route of compound exposure. This finding suggests that short-term, less expensive studies may be useful in identifying kidney carcinogens.

啮齿动物的床上用品，饮食和饮用水可能包含影响NTP测试计划的相同终点的化合物，例如繁殖和开发。例如，内毒素（霉菌的副产品）可以掩盖对暴露于哮喘的剂的反应。同样，啮齿动物饮食中的植物雌激素可以掩盖对暴露于雌激素化合物的反应。我们正在与NIEHS质量保证实验室合作，以量化这些效果，并制定啮齿动物研究污染物限制的指南。我们为一项多局部小鼠研究的研究设计做出了贡献，其中不同的菌株暴露于电离辐射，然后跟踪肿瘤的发展。选择这些菌株代表广泛的遗传变异。尽管数据尚未完成，但早期的迹象表明，不同的菌株对辐射具有一定的敏感性，并显示出不同的位置和肿瘤速率。一些化合物导致暴露两年的大鼠肾脏肿瘤。但是，为期两年的研究是昂贵且耗时的。我们已经确定了早期发作肾脏病变，这些病变可能预测了大鼠的较晚肾脏肿瘤。通过评估来自许多先前NTP研究的数据，我们证实了早期病变和肾脏肿瘤之间的关联，并表明该关联不受饮食类型或复合暴露途径的影响。这一发现表明，短期，较便宜的研究可能有助于识别肾脏致癌物。