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

• 批准号: 8149007
• 负责人: grace e kissling
• 金额: $ 9.61万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 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/8149007
• 关键词: Rodent; Source

Rodent bedding 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. We are working with the Quality Assurance Laboratory to quantify these effects and develop guidelines for limits on contaminants in bedding of rodent studies. The ability of acrylamide, a compound found in heated cooking oils, to interfere with reproduction in rodents has been well-established. We fed male mice diets containing either 10% fat or 60% fat, creating groups of lean or obese male mice, respectively. We then showed that obesity in male mice greatly exacerbated the reproductive toxicity of acrylamide. Obese males exposed to acrylamide produced fewer and smaller litters than males that were lean and exposed to acrylamide or that were obese or lean and not exposed to acrylamide. 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.

啮齿动物的床上用品可能包含影响NTP测试程序（例如繁殖和开发）目标的相同终点的化合物。 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。 我们正在与质量保证实验室合作，以量化这些效果，并制定指南，以限制啮齿动物研究中污染物的限制。 丙烯酰胺是加热食用油中发现的一种化合物，干扰啮齿动物繁殖的能力。 我们分别喂养含有10％脂肪或60％脂肪的雄性小鼠饮食，分别产生一组瘦或肥胖的雄性小鼠。 然后，我们表明雄性小鼠的肥胖大大加剧了丙烯酰胺的生殖毒性。 暴露于丙烯酰胺的肥胖雄性产生的垃圾越来越小，比瘦弱或暴露于丙烯酰胺的雄性或肥胖或瘦的男性且不暴露于丙烯酰胺。 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。