| Co-Investigator(Kenkyū-buntansha) |
KIZU Ryoichi Kanazawa University, Graduate School of Natural Science and Technology, Associate Professor, 大学院・自然科学研究科, 助教授 (80143915)
HAYAKAWA Kazuichi Kanazawa University, Graduate School of Natural Science and Technology, Professor, 大学院・自然科学研究科, 教授 (40115267)
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| Budget Amount *help |
¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 2002: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Research Abstract |
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
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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
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