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，柴油机尾气颗粒物（DEPE）和DEPE成分之一的多环芳烃（PAH）的雌激素和抗雌激素作用得到了澄清。今年，对 DEPE 和 PAH 的雄激素和抗雄激素活性进行了检查。通过将DEPE应用于人PC3/AR培养细胞中的荧光素酶报告基因检测，DEPE不显示雄激素活性，但显示抗雌激素活性。 DEPE 中包含的几种具有 4 或 5 环的多环芳烃显示出很强的抗雄激素活性。 DEPE和PAHs均具有4或5环，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DEPE中包含的PAH。此外，几种硝基多环芳烃在酵母双杂交测定中显示出雄激素活性。接下来，为了增加单羟基多环芳烃 (OHPAH) 作为分析物的数量，我们修改了 HPLC/荧光检测方法的条件。并且，为了分析尿液中的 OHPAH 及其结合物，开发了包括水解结合物的预处理方法。结果，吸烟者尿样中2-羟基芴的尿浓度高于非吸烟者，证明2-羟基芴是比1-羟基芘更有效的吸烟生物标志物。泰国受试者的尿液 OHPAH 浓度高于日本受试者。造成这种情况的一个可能原因是泰国房屋室内使用的木柴燃料产生的烟雾。