MOLECULAR TOXICOLOGY GENE EXPRESSION AND CELL DEATH

描述：（改编自研究者摘要）：长期 暴露于环境和药物毒物是一种健康风险， 人口。 然而，调查人员识别 潜在的风险已经超出了他们量化风险的能力。 一些 环境疾病的发生可能是由于基因的微妙变化， 表情 因此，估计与人类接触有关的风险 需要测量基因表达时的反应， 会导致累积性损害 这项提案的长期目标是 就是找出毒物改变基因表达的机制 这些病理学的基础。 特别是，研究人员将 解决这个问题，“c-myc基因是毒物诱导的靶点吗？ 基因表达和c-myc激活的后果是什么， 有毒物质？“对肾脏上皮细胞的初步研究表明， c-myc被有毒物质激活，包括S-（1，2-二氯乙烯基）-L- 半胱氨酸（DCVC），环境污染物的代谢物， 工业溶剂三氯乙烯和下游靶基因 因此被打开。 此外，这些影响可能 通过与MAX和MAD蛋白的相互作用来调节， 与myc相同的转录因子蛋白家族。 因为c-myc 已知表达介导包括细胞死亡在内的过程 （凋亡），毒物诱导的c-myc表达的变化可能有助于 肾脏或其他器官的损伤。 拟议的研究将开始 以确定可能导致长期疾病的早期分子变化， 化学品暴露对健康的影响。 建议基本 研究将确定暴露于有毒物质的离散基因靶点。 这些目标可能提供一种手段，生物测定早期人类接触 以便在受影响人群中监测早期反应。 因此，在本发明中， 本申请的长期目标是使用分子技术 了解人类接触毒品和化学品的风险。

DESCRIPTION: (Adapted from the Investigator's Abstract): Long term exposure to environmental and drug toxicants is a health risk to the human population. However, the investigator's ability to identify potential risks has outstripped their ability to quantify the risk. Some environmental diseases may occur due to subtle changes in gene expression. Thus, estimating the risk associated with human exposure requires measurement of responses during the time when gene expression is leading to cumulative damages. The long term goal of this proposal is to identify mechanisms by which toxicants change expression of genes underlying these pathologies. In particular the investigator will address the question, "Is the c-myc gene a target for toxicant induced gene expression and what are the consequences of c-myc activation by the toxicants?" Preliminary studies, in kidney epithelial cells suggest that c-myc is activated by toxicants including S-(1,2-dichlorovinyl)-L- cysteine (DCVC), a metabolite of the environmental contaminant and industrial solvent trichlorethylene, and that downstream targets genes are turned on as a result. Moreover, it appears that these effects may be regulated by interactions with MAX and MAD proteins, members of the same family of transcription factor proteins as myc. Because c-myc expression is known to mediate processes including cell death (apoptosis), toxicant induced changes in c-myc expression may contribute to damage in the kidney or other organs. Proposed studies will begin to identify the early molecular changes which may lead to long term health effects of chemical exposure. It is suggested that basic research will identify discrete gene targets for toxicant exposure. These targets may provide a means to bioassay early human exposure allowing early responses to be monitored in exposed populations. Thus, the long term goal of this application is to use molecular technology to understand the risk of human exposure to drugs and chemicals.