Identifying And Evaluating Sources Of Variability In Rod

识别和评估杆变异的来源

• 批准号: 6504695
• 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/6504695
• 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, following a detailed histopathological examination, we examined the lobe-specific incidences and degrees of severity of background prostatic, seminal vesicular, and ampullary glandular lesions in 1768 control Fischer 344 rats from 35 recent National Toxicology Program (NTP) two-year rodent bioassays carried out at four different laboratories. Inflammation in the dorsolateral lobes was significantly correlated with pituitary gland adenoma, and prolactin was suggested to play an important role in the pathogenesis of prostatic inflammation. Significant lab-to-lab variability in the amount of tissue sampled was also observed, and we suggested an optimal embedment and trimming method in rat prostate and seminal vesicle to ensure adequate and consistent sampling. In another project, we investigated the factors affecting inter-scorer and inter-laboratory variability in response in the mouse epididymal sperm aneuploidy (mESA) assay. We identified microscope scoring criteria as the major source of interlaboratory variation, which emphasizes the importance of strict technical controls for this assay. Several years ago the NTP developed and adopted a new rodent diet (NTP-2000), a diet higher in fiber and lower in protein than the previously used NIH-07 diet. Data are accumulating which will allow the comparison of tumor incidence, body weight, and survival in animals fed this new diet with animals fed the NIH-07 diet. This ongoing investigation will help the NTP decide whether or not additional measures such as dietary restriction are needed in its long term rodent bioassays to reduce body weight to an acceptable level and to lower background tumor rates.

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，在详细的组织病理学检查之后，我们检查了1768只对照Fischer 344只大鼠的脑叶特异性发病率和背景前列腺、精囊和壶腹腺病变的严重程度，这些大鼠来自35个国家毒理学计划（NTP）最近在四个不同的实验室进行的为期两年的啮齿动物生物测定。背外侧叶炎症与垂体腺瘤有显著相关性，提示催乳素在前列腺炎症的发病机制中起重要作用。实验室间取样组织的数量也存在显著差异，我们建议在大鼠前列腺和精囊中采用最佳的埋置和修剪方法，以确保取样的充分和一致。在另一个项目中，我们研究了影响小鼠附睾精子非整倍体（mESA）测定中评分者和实验室间反应变异性的因素。我们确定显微镜评分标准是实验室间差异的主要来源，这强调了严格技术控制的重要性。几年前，国家毒理学规划制定并采用了一种新的啮齿动物饮食（NTP-2000），这种饮食比以前使用的NIH-07饮食纤维含量更高，蛋白质含量更低。正在积累的数据将使用这种新饲料喂养的动物与用NIH-07饲料喂养的动物的肿瘤发病率、体重和存活率进行比较。这项正在进行的调查将有助于国家毒理学规划决定是否需要在其长期啮齿动物生物测定中采取额外措施，如饮食限制，以将体重降低到可接受的水平并降低背景肿瘤率。