Identifying And Evaluating Sources Of Variability In Rod

该项目的目标是确定和评估实验室研究中可能影响反应变异性的因素。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分析评分间和实验室间可变性的主要因素。这一发现强调了对这项检测进行严格的技术控制的重要性，包括控制用于治疗引起的精子数量减少的载玻片准备，以及对载玻片进行编码以避免微妙的记分器偏差。 另一项研究表明，在雄性Fisher 344大鼠中，肺纤维化和炎症与肾上腺嗜铬细胞瘤的发生有关。这种关联(在剂量组和对照动物中都很明显)可能有助于解释不同研究之间以及剂量组和对照组之间观察到的嗜铬细胞瘤发病率的差异。 我们还评估了高效参比激动剂乙炔雌二醇在子宫滋养试验中的实验室间变异性。比较幼龄雌性大鼠和成年去卵巢大鼠两种模型的差异。对于被评估的单一化合物，这两种模型似乎都是健壮的、可重复性的，并可在实验室之间转移。 最后，我们比较了Peto和Poly-k试验在检测啮齿动物致癌性方面的性能。如果死因可以可靠地确定，那么皮托测试是合理的。然而，如果这样的信息是不准确的，那么皮托测试可能会非常具有误导性。Poly-k检验不需要死因信息，因此当无法获得准确的死因信息时，它是Peto检验的一个有吸引力的替代方法。

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.