Genetic Alterations In Rodent Cancer

细胞和分子病理学分支的科学家与NIEHS的科学家合作，正在进行系统的努力，以确定B6C3F1小鼠和NTP大鼠模型中自发和化学诱导肿瘤最常见位点的癌基因和肿瘤抑制基因的遗传改变。我们的目标是提高我们对标准啮齿动物模型暴露于环境化学物质后发现的肿瘤发病率增加的重要性的理解。了解化学诱导的啮齿动物肿瘤中存在的遗传改变谱，它们在肿瘤前病变到肿瘤发展过程中的时间表现，以及这些因素在组织与组织之间和化学物质与化学物质之间的差异，将为区分自发肿瘤和化学诱导肿瘤提供分子基础。该方法主要通过内部协作来完成。从前瞻性和回顾性研究中从对照和化学处理的啮齿动物的肿瘤中分离出DNA和RNA，并使用基于PCR的分析方法分析遗传改变。回顾性研究从以前的生物分析中确定肿瘤的特定遗传改变，主要通过基于pcr的分析来检查档案材料。这些研究旨在将化学特异性特性（结构特征/遗传毒性/代谢）与特定靶器官的肿瘤前病变和肿瘤病变中存在的遗传改变谱特征联系起来。这提供了一个比较化学物质类别的机会，评估一类化学物质的结构/活性关系，以及评估特定目标组织对不同化学物质的反应，而无需重复长期研究。更重要的是，国家毒理学规划研究产生的数据提供了对癌症及其与人类关系的分子理解。

A systematic effort is being made by Cellular and Molecular Pathology Branch scientists in collaboration with NIEHS scientists to identify genetic alterations in oncogenes and tumor suppresser genes in the most frequent sites for spontaneous and chemical-induced neoplasms in B6C3F1 mice and NTP rat models. The goal is to increase our understanding of the significance of increased incidence of neoplasms that are found following exposure of our standard rodent models to environmental chemicals. Knowledge of the spectrum of genetic alterations that are present in chemically induced rodent tumors, their temporal appearance in the progression from preneoplastic lesions to neoplasms, and the way in which these factors may differ from tissue-to-tissue and chemical-to-chemical, will provide a molecular basis for distinguishing between spontaneous and chemically induced neoplasms. The approach is accomplished primarily from in-house collaborations. DNA and RNA are isolated from neoplasms in control and chemically treated rodents from prospective and retrospective studies and analyzed for genetic alterations using PCR based assays. Retrospective studies to identify specific genetic alterations in neoplasms from previous bioassays involve examination of archival material primarily through PCR-based assays. These studies are being designed to correlate chemical-specific properties (structural features/genotoxicity/metabolism) with characteristics of the spectrum of genetic alterations present in preneoplastic and neoplastic lesions of specific target organs. This provides an opportunity to compare classes of chemicals, to evaluate structure/activity relationships within a class, and to evaluate the response of specific target tissues to different chemicals, without having to repeat the long-term studies. More importantly the data generated from NTP studies provide a molecular understanding of cancer and its relevance to humans.