Study on Endocrine Disruption of Polycyclic Aromatic Hydrocarbons and Their Metabolites and Its Assay

多环芳烃及其代谢物的内分泌干扰作用及其含量测定研究

基本信息

批准号：
14370728
负责人：
HAYAKAWA Kazuichi
金额：
$ 9.02万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

Last year, both estrogenic and antiestrogenic actions of diesel exhaust particulate(DEPE) and polycyclic aromatic hydrocarbon(PAH), which was one of the constituent of DEPE, were clarified. This year, both androgenic and antiandrogenic activities of DEPE and PAH were examined. By applying DEPE to the luciferase reporter gene assay in human PC3/AR culture cells, DEPE did not show androgenic activity but antiestrogenic activity. Several PAHs having 4 or 5 rings, which are included in DEPE, showed strong antiandrogenic activity. Both DEPE and PAHs having 4 or 5 rings, were also agonists of human allyl hydrocarbon receptor(AhR). These results suggested that DEPE showed antiandrogenic activity and that a part of this activity was derived from PAHs which were included in DEPE. In addition, several nitropolycyclic aromatic hydrocarbons showed aniandorgenic activity in the yeast two-hybrid assay. Next, to increase the number of monohydroxy polycyelic aromatic hydrocarbons(OHPAH) as analytes, conditions of our HPLC/fluorimetric detection method were modified. And, to anayze both urinary OHPAHs and their conjugates, the pretreatment method including hydrolysis of the conjugates was developed. As the result, the urinary concentration of 2-hydroxyfluorene in smokers' urine samples was higher than that in nonsmokers', and it was proven that 2-hydroxyfluorene was a more effective biomarker for smoking than 1-hydroxypyrene. Urinary OHPAH concentrations of Thai subjects were higher than those of Japanese. As a possible reason for this, the smoke of the firewood fuel used in the indoor of Thai house was considered.

去年，阐明了柴油排气颗粒物（DEPE）和多环芳烃（PAH）的雌激素和抗源性作用，这是DEPE的组成部分之一。今年，检查了DEPE和PAH的雄激素和抗雄激素活性。通过将DEPE应用于人PC3/AR培养细胞中的荧光素酶报告基因测定，DEPE没有显示出雄激素活性，而是显示抗雌激素活性。几个具有4或5个环的PAH，其中包含在DEPE中，显示出强烈的抗二手活性。具有4或5个环的DEPE和PAH也是人烯丙基烃受体（AHR）的激动剂。这些结果表明，DEPE表现出抗雄激素活性，并且该活性的一部分源自PAH，其中包括在DEPE中。此外，几种硝基循环芳烃在酵母双杂化测定中显示出肛门二氧化活性。接下来，为了增加单羟基多酰胺芳烃（OHPAH）的数量，作为分析物，我们的HPLC/荧光检测方法的条件得到了修改。而且，对于Anayze均尿路OHPAH及其偶联物，开发了包括结合物水解的预处理方法。结果，吸烟者的尿液样品中2-羟基氟烯的尿液浓度高于非吸烟者的尿液，并且证明2-羟基氟氟烯比1-羟基苯乙烯更有效地吸烟。泰式受试者的尿型OHPAH浓度高于日本人。为此，考虑了泰国房屋室内使用的柴火燃料的烟雾。