Identifying And Evaluating Sources Of Variability In Rod

识别和评估杆变异的来源

• 批准号: 6672917
• 负责人: JOSEPH K HASEMAN
• 金额: --
• 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/6672917
• 关键词: bioassay; biological polymorphism; carcinogen testing; carcinogenesis; dietary fiber; dietary proteins; dietary restriction; histopathology; laboratory rat; longitudinal animal study; neoplasm /cancer epidemiology; nutrition related neoplasm /cancer; nutrition related tag; pituitary hormones; prolactin; prostate preneoplastic state; tissue /cell preparation; veterinary science

The goal of this project is to identify and evaluate factors that may influence variability in response in laboratory studies. For example, we found that differences in scoring criteria was the major factor that produced inter-scorer and inter-laboratory variability for the mouse epididymal sperm aneuploidy assay. This finding emphasizes the importance of strict technical controls for this assay, including controlling slide preparations for treatment-induced reductions in sperm count and coding slides to avoid subtle scorer bias. Another investigation demonstrated an association between lung fibrosis and inflammation and the occurrence of adrenal pheochromoctyoma in male Fisher 344 rats. This association (which was evident both in dosed and control animals) may help explain the variability in pheochromocytoma incidence observed from study to study and between dosed and control groups. We also evaluated the inter-laboratory variability in response in the uterotrophic assay for a high-potency reference agonist, ethinyl estradiol. Two model systems were compared: the immature female rat and the adult ovariectomized rat. Both models appeared to be robust, reproducible and transferable across laboratories for the single compound evaluated. Finally, we compared the performance of the Peto and Poly-k tests for detecting rodent carcinogenicity. If cause of death can be reliably determined, then the Peto test is reasonable. However, if such information is inaccurate, then the Peto test can be quite misleading. The Poly-k test does not require cause of death information, and is thus an attractive alternative to the Peto test when accurate cause of death information is unavailable.

该项目的目标是识别和评估可能影响实验室研究中反应变异性的因素。例如，我们发现评分标准的差异是产生小鼠附睾精子非整倍体测定的评分者和实验室间差异的主要因素。这一发现强调了严格技术控制的重要性，包括控制治疗引起的精子数量减少的载玻片制备和编码载玻片以避免细微的评分偏差。