| Project/Area Number |
14370728
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
HAYAKAWA Kazuichi Kanazawa University, Graduate School of Natural Science and Technology, Ph.D., Professor, 自然科学研究科, 教授 (40115267)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOI Tsuyoshi Kanazawa University, Graduate School of Medical Science, Ph.D., Professor, 医学系研究科, 教授 (70135226)
TORIBA Akira Kanazawa University, Faculty of Pharmaceutical Sciences, Ph.D., Assistant Professor, 薬学部, 助手 (50313680)
KIZU Ryoichi Kanazawa University, Graduate School of Natural Science and Technology, Ph.D., Associate Professor, 自然科学研究科, 助教授 (80143915)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥10,700,000 (Direct Cost: ¥10,700,000)
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| Keywords | polycyclic aromatic hydrocarbon / diesel exhaust particulate / androgen / antiandrogen activity / monohydroxylated polycyclic aromatic hydrocarbon / east two-hybrid assay / HPLC / fluoresecnce detection / urine / smoking / エストロゲン様 / 抗エストロゲン活性 / モノヒドロキシ体 |
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| Research Abstract |
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.
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