GENETIC ANALYSIS OF CANCER IN HUDSON RIVER TOMCOD

描述：(改编自申请者摘要)：哈德逊河(纽约) 鳕鱼是一种野生鱼类，发病率很高(90%)。 自然发生的肝细胞癌。申请人已被 研究哈德逊河鳕鱼致癌的分子生物学，以及 在这些肿瘤中发现了K-ras癌基因的频繁激活。在……里面 在这份申请书上，申请人提议用这个来延长他的学业 有价值的模型系统来研究与以下相关的几个关键问题 环境导致的鱼类癌症。他将进行实验，以 定义暴露时与癌症风险最相关的生命阶段 有机体。利用现代方法扩增特定基因 序列(PCR)他将决定癌基因是否可以被激活 在可追溯到本世纪初的博物馆标本中被发现。 这些研究应该有助于澄清最近环境保护的作用 哈德逊河退化中的鳕鱼致癌率。他将继续追查 他的初步发现表明，生活在哈德逊河中的鳕鱼 表现出高水平的细胞色素P450基因表达，并将 调查这一现象在导致 致癌反应。最后，他将用鱼培育细胞系。 从哈德逊河鳕鱼和缅因州分离的肿瘤和正常组织 大头鳕鱼，这表明癌症发病率很低。这里描述的研究将 进一步阐明了鳕鱼致癌的病因，并进一步 开发一种有用的自然异种种群致癌模型。 他还希望这项研究能提供可用于研发的数据 环境退化和恢复的新分子生物标志物。

DESCRIPTION: (Adapted from applicant's abstract): Hudson River (NY) tomcod are a feral fish population with a very high incidence (90 percent) of naturally occurring hepatocellular carcinoma. The applicant has been studying the molecular biology of Hudson River tomcod carcinogenesis, and has found frequent activation of the K-ras oncogene in these tumors. In this application, the applicant proposes to extend his studies using this valuable model system to investigate several critical issues related to environmentally induced cancer in fish. He will perform experiments to define the life stage at exposure most relevant to cancer risk in these organisms. Using modern methods of amplification of specific gene sequences (PCR) he will determine whether oncogene activation can be detected in museum specimens dating back to the early part of the century. These studies should help to clarify the role of recent environmental degradation of the Hudson River in the tomcod cancer rate. He will pursue his preliminary findings that suggest that tomcod living in the Hudson exhibit a high level of cytochrome P450 gene expression, and will investigate the possible role of this phenomenon in contributing to the carcinogenic response. Finally, he will develop cell lines from fish tumors and normal tissue isolated from Hudson River tomcod and from Maine tomcod, which show a low cancer incidence. The studies described here will shed further light on the etiology of tomcod carcinogenesis and further develop a useful model for carcinogenesis in natural out-bred populations. He also expects this research to provide data that can be used to develop new molecular biomarkers for environmental degradation and recovery.