HEPATOTOXICITY OF ATRAZINE AND ITS DEGRADATION PRODUCTS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。阿特拉津是世界上使用最多的除草剂之一。本研究的重点是研究阿特拉津及其降解产物的肝毒性。在2006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相代谢物。为此，我们实验室开发了基于高效液相色谱-质谱仪的分析方法，并在本实验室进行了应用。在37℃下与大鼠肝微球孵育2小时后，利用基于串联质谱仪的分析方法检测阿特拉津的降解产物，包括去乙基阿特拉津和去异丙基阿特拉津。这是首次在该生物培养系统中检测到这些阿特拉津降解产物。在过去的一年里，我们还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的影响，以便更准确地评价阿特拉津及其降解产物的肝毒性。这一组的五家同行评审的出版物在这一资助期承认了RCMI赠款(12RR13459)。明年，我们计划继续利用我们实验室建立的高效液相-质谱联用程序对阿特拉津在大鼠肝微粒体中的I相代谢物进行研究。新发现的阿特拉津降解产物的肝脏毒性将进行评估，并与其母体化合物进行比较研究。本研究将重点研究这些农药对NADPH诱导的大鼠肝微粒体培养体系中脂质过氧化的影响。

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.