The research on the evaluation method for the endocrine-disrupting effect of benzo[a]pyrene and its metabolites

据报道，苯并[a]芘（BaP）等多环芳烃（PAHs）具有内分泌干扰活性，主要是其抗雌激素特性。本研究对多环芳烃及其类似物（代谢物）的内分泌干扰活性进行了研究。几种含有BaP的多环芳烃具有抗雌激素和抗雄激素的作用，推测多环芳烃通过激活芳烃受体（AhR）发挥抗雌激素和抗雄激素的作用。另一方面，还检查了BaP代谢产物的雌激素和抗雌激素作用。苯并（a）芘的单羟基衍生物（OHBaPs）具有雌激素样或抗雌激素样作用，而苯并（a）芘的二醇和醌类衍生物则无此作用。因此，苯并（a）芘代谢产物中酚羟基的存在和位置在诱导内分泌干扰活性中起重要作用。 ...更多信息 多环芳烃及其代谢物的多分泌干扰作用。为评价大气中多环芳烃的吸入暴露，对3个城市大气颗粒物中多环芳烃的浓度进行了测定。城市中多环芳烃的浓度（即暴露剂量）远高于郊区，城市中多环芳烃的主要贡献者被认为是汽车、家庭供暖系统（如炉子和煤油加热器）、发电厂和焚烧炉。然而，多环芳烃的摄入量取决于个人的生活方式，如饮食和吸烟，因此，生物监测是一个特别有价值的方法来提供多环芳烃的暴露数据。以尿中苯并（a）芘等多环芳烃代谢产物为生物标志物。1-，3-，9-OHBaPs是BaP在体外的主要代谢产物。建立了高效液相色谱-荧光检测法同时测定OHBaPs、1-羟基芘（1-OHP）和2-羟基芴（2-OHF）的方法。在受试者的尿中检测到具有特别高的雌激素活性的3-OHBaP。此外，吸烟对多环芳烃暴露的影响进行了研究，使用尿中1-OHP和2-OHF的浓度。吸烟者尿1-OHP和2-OHF水平显著高于非吸烟者。因此，尿中多环芳烃代谢物可能是评价多环芳烃暴露的敏感和特异的生物标志物。少

Polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (BaP) have been reported for their endocrine-disrupting activities, primarily their antiestrogenic characteristics. In this study, the endocrine-disrupting activities of PAHs and their analogues (metabolites) were investigated. Several PAHs containing BaP exhibited the antiestrogenic and antiandrogenic effects and it was suggested that the PAHs act as antiestrogens and antiandrogens by activating the aryl hydrocarbon receptor (AhR). On the other hand, the estrogenic and antiestrogenic effects of the BaP metabolites were also examined. Monohydroxy derivatives of BaP (OHBaPs) exhibited the estrogenic or antiestrogenic effects, diol and quinone derivatives of BaP did not. Therefore, the presence and position of phenolic hydroxy group in the BaP metabolites play an important role in the induction of the endocrine-disrupting activities.Two methods for the evaluation of PAH exposure were developed to assess a human risk of the en … More docrine-disrupting effects for PAHs and their metabolites. To evaluate the exposure to PAHs from ambient air by inhalation, the atmospheric concentrations of PAHs were measured with the airborne particulates collected in three cities. The concentrations of PAHs, that is, the exposure dose were much higher in urban area than in suburban area, and the main contributors of PAHs in urban area were considered to be automobiles, domestic heating systems such as furnaces and kerosene heaters, power plants and incinerators. However, the intake of PAHs depends on individual lifestyle such as diet and tobacco smoke, therefore, biomonitoring is an especially valuable method to provide exposure data of PAHs. Urinary metabolites of PAHs including BaP were used as PAH biomarkers. 1-, 3-, 9-OHBaPs were identified as major metabolites of BaP in vitro by human recombinant cytochrome P450. The methods for determining OHBaPs, 1-hydroxypyrene (1-OHP) and 2-hydroxyfluorene (2-OHF) using high-performance liquid chromatography with fluorescence detection were developed. 3-OHBaP, which has a particularly high estrogenic activity, was detected in the urine of a subject. Further, the effect of smoking on the exposure to PAHs was investigated using the concentrations of urinary 1-OHP and 2-OHF. The urinary 1-OHP and 2-OHF levels in smokers were significantly higher than those in non-smokers. Thus, urinary metabolites of PAHs may be sensitive and specific biomarkers for the assessment of the exposure to PAHs. Less