GENETIC ANALYSIS OF CANCER IN HUDSON RIVER TOMCOD

描述：（改编自申请人摘要）：哈德逊河（纽约州） 小鳕是一种野生鱼类种群，发病率非常高（90%） 自然发生的肝细胞癌。 申请人已 研究哈德逊河小鳕致癌作用的分子生物学， 发现K-ras癌基因在这些肿瘤中频繁激活。 在 在此申请中，申请人建议使用此 有价值的模型系统，以调查有关的几个关键问题， 环境诱发的鱼类癌症。 他将进行实验， 定义生命阶段中与癌症风险最相关的暴露， 有机体 利用现代方法扩增特定基因 序列（PCR）他将确定癌基因激活是否可以 在博物馆标本中发现的，可以追溯到世纪早期。 这些研究应该有助于澄清最近环境变化的作用。 哈德逊河在小鳕癌症发病率方面的退化。 他要追赶 他的初步发现表明生活在哈德逊河的小鳕 表现出高水平的细胞色素P450基因表达， 研究这种现象在促进 致癌反应 最后，他将从鱼类中培育细胞系 从哈德逊河小鳕和缅因州分离的肿瘤和正常组织 小鳕鱼，癌症发病率低。 这里描述的研究将 进一步阐明了小鳕致癌的病因， 开发一个有用的模型，在自然远系繁殖人群的致癌作用。 他还预计这项研究将提供可用于开发的数据 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.