Identifying And Evaluating Sources Of Variability In Rod

本项目的目标是确定和评价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后，我们检查了1768只对照Fischer 344大鼠的背景前列腺、精囊和壶腹腺病变的特定叶发生率和严重程度，这些大鼠来自最近在四个不同实验室进行的35项国家毒理学计划（NTP）两年啮齿动物生物测定。垂体腺瘤与前列腺背外侧叶炎症密切相关，催乳素在前列腺炎症的发生中起重要作用。还观察到组织取样量的显著实验室间差异，我们建议在大鼠前列腺和精囊中采用最佳包埋和修剪方法，以确保充分和一致的取样。 在另一个项目中，我们研究了影响小鼠附睾精子非整倍性（梅萨）试验中评分者间和实验室间反应变异性的因素。我们确定了显微镜评分标准作为实验室间变异的主要来源，这强调了严格技术控制的重要性。 几年前，NTP开发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。数据正在积累，这将允许比较喂食这种新饮食的动物与喂食NIH-07饮食的动物的肿瘤发病率、体重和存活率。这项正在进行的研究将帮助NTP决定在其长期啮齿动物生物测定中是否需要采取额外措施（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发生率。

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.