MOLECULAR MECHANISMS OF CARCINOGENESIS IN FERAL FISH

近100%的哈德逊河老鳕鱼表现出组织学上的定义 肝细胞癌，而这种情况在鳕鱼中不存在 来自干净的航道环境。这些肿瘤的病因学 鱼是未知的。然而，哈德逊河历史上一直是 受到更高程度的环境侮辱， 已知的哺乳动物致癌物质。增加了对癌症发生的认识 鱼类有可能增加我们对这一过程的理解 在所有脊椎动物中诱发癌症，并可能导致描述 适合致癌检测的替代物种。而其他人 工作人员已经解决了环境致癌的根源问题 野生鱼类种群，调查遗传方面的 这些生物体中缺少肿瘤。这项研究将评估 哈德逊河致癌过程中的分子遗传学机制 托马科德。 具体地说，我们将确定哈德逊河鳕鱼是否构成 具有遗传程序性倾向的分离种群 对肿瘤或对环境致癌物的敏感性增加。这 将通过使用线粒体DNA分析和 不同接触人群鱼类中肿瘤发病率的测定 清洁或哈德逊河环境。此外，我们还将探索 哈德逊已知和新的鱼类癌基因的潜在激活 托马德河。这种方法将涉及一系列的转基因 鳕鱼DNA导入NIH3T3细胞及其与裸鼠共转染的研究 化验。将对转化的细胞进行外源鱼类DNA检测 用Southern杂交鉴定序列和癌基因。 激活的癌基因将根据它们的 激活机制和新的癌基因将被克隆和 特色化的。

Close to 100% of older Hudson River tomcod exhibit histologically defined hepatocellular carcinomas, whereas this condition is absent in tomcod from a clean waterway environment. The etiology of neoplasia in these fishes is unknown. However, the Hudson River has historically been subject to elevated levels of environmental insult with a multitude of known mammalian carcinogens. Increased knowledge of carcinogenesis in fishes has the potential to increase our understanding of the process of cancer induction in all vertebrates, and may result in the description of alternate species suitable for carcinogenesis testing. While other workers have addressed the environmental origin of carcinogenesis in feral fish populations, investigations on the genetic aspects of neoplasia in these organisms are lacking. This study will evaluate molecular genetic mechanisms in the carcinogenic process in Hudson River tomcod. Specifically, we will determine if Hudson River tomcod constitute a separate population with either a genetically programmed predisposition to neoplasia or increased sensitivity to environmental carcinogens. This will be accomplished through the use of mitochondrial DNA analysis and determination of tumor incidence in fish from each population exposed to clean or Hudson River environments. In addition, we will explore the potential activation of both known and novel fish oncogenes in Hudson River tomcod. This approach will involve a series of transfections of tomcod DNA into NIH3T3 cells and use of the nude mouse co-transfection assay. Transformed cells will be assayed for exogenous fish DNA sequences and oncogenes identified by use of Southern blot hybridization. Activated oncogenes will be characterized with respect to their mechanisms of activation and novel oncogenes will be cloned and characterized.