HEPATOTOXICITY OF ATRAZINE AND ITS DEGRADATION PRODUCTS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。阿特拉津是世界上使用最多的除草剂之一。本论文主要研究阿特拉津及其降解产物的肝毒性。在2005年6月至2006年5月的资助期间，我们研究了阿特拉津在大鼠肝微粒体孵育系统中的代谢，以确定阿特拉津的主要I相代谢产物。基于HPLC-MS/MS的分析方法被开发并在我们的实验室用于这些目的。在37 ℃下与大鼠肝微粒体孵育2小时后，通过使用有利的基于串联质谱的分析方法检测阿特拉津降解产物，包括脱乙基阿特拉津和脱异丙基阿特拉津。这是首次在该生物培养系统中检测到阿特拉津降解产物。在过去的一年里，我们也开始研究阿特拉津及其降解产物对Fe（III）-NADPH诱导的大鼠肝微粒体脂质过氧化反应的影响，以便更准确地评估阿特拉津及其降解产物的肝毒性。来自该小组的五篇同行评审出版物在此资助期间承认了RCMI赠款（12 RR 13459）。 明年，我们计划利用本实验室建立的HPLC-MS/MS方法，继续对阿特拉津在大鼠肝微粒体中的I相代谢产物进行研究。将评估新鉴定的阿特拉津降解产物的肝毒性，并与其母体化合物进行比较研究。本研究旨在探讨这些农药对NADPH诱导的大鼠肝微粒体孵育体系脂质过氧化反应的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Atrazine is one of the herbicides that are most heavily used in the world. The proposed research is focused on studying the hepatotoxicity of atrazine and its degradation products. In the funding period from 6/05 to 5/06, we studied the metabolism of atrazine in rat liver microsome incubation system to identify the major phase I metabolites of atrazine. HPLC-MS/MS based analytical methods were developed and used in our lab for these purposes. After incubation with rat liver microsome for 2 hours at 37 0C, atrazine degradation products including deethylatrazine and deisopropylatrazine were detected by using an advantageous tandem mass spectrometry-based analytical method. This was the first report on the detection of these atrazine degradation products in this biological incubation system. This past year we also started to study the effects of atrazine and its degradation products on Fe(III)-NADPH induced lipid peroxidation in rat liver microsome so that hepatotoxicity of atrazine and its degradation products would be more precisely assessed. Five peer-reviewed publications from this group are acknowledging the RCMI grant (12RR13459) in this funding period. Next year, we plan to continue the study on phase I metabolites of atrazine in rat liver microsome using the HPLC-MS/MS procedures established in our lab. Hepatotoxicity of newly identified atrazine degradation products will be assessed and comparatively studied against their parent compounds. The study will be focused on the effects of these agrochemicals on NADPH induced lipid peroxidation in rat liver microsome incubation system.