Genetic Alterations In Rodent Cancer

细胞和分子病理学分支的科学家正在与NTP/NIEHS的科学家合作，通过全基因组分析和其他遗传学方法，在B6 C3 F1小鼠和NTP大鼠模型中自发性和化学诱导肿瘤的最常见部位，系统地鉴定可能在癌症中发挥作用的癌基因、肿瘤抑制基因和主要基因的遗传学改变。 我们的目标是增加我们的理解的重要性增加的发病率的肿瘤，发现我们的标准啮齿动物模型暴露于环境化学品。了解化学诱导的啮齿动物肿瘤中存在的遗传改变或基因组改变的谱，其在从癌前病变到肿瘤进展中的时间表现，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可能不同的方式，将为区分自发性肿瘤和化学诱导的肿瘤提供分子基础。 该方法主要通过内部合作实现。 从前瞻性和回顾性研究的对照和化学处理的啮齿动物的肿瘤中分离DNA和RNA，并使用基于PCR的测定和基因组分析来分析遗传改变。 回顾性研究，以确定特定的遗传变异的肿瘤，从以前的生物测定涉及检查档案材料，主要是通过基于PCR的测定或全基因组分析。 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相关联。 这提供了一个机会来比较化学品的类别，以评估一类内的结构/活性关系，并评估特定靶组织对不同化学品的反应，而不必重复长期研究。更重要的是，NTP研究产生的数据提供了对癌症及其与人类相关性的分子理解。

A systematic effort is being made by Cellular and Molecular Pathology Branch scientists in collaboration with NTP/NIEHS scientists to identify genetic alterations in oncogenes and tumor suppresser genes and major genes which may play a role in cancer by genome wide analysis and other genetic methods 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 or genomic 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 and genomic analysis. Retrospective studies to identify specific genetic alterations in neoplasms from previous bioassays involve examination of archival material primarily through PCR-based assays or genome wide analysis. 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.