Okamura Kazumasa, Kizu Ryoichi, Toriba Akira, Murahashi Tsuyoshi, Mizokami Atsushi, Burnstein Kerry L, Klinge Carolyn M, Hayakawa Kazuichi
Graduate School of Natural Science and Technology, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-0934, Japan.
Toxicology. 2004 Feb 15;195(2-3):243-54. doi: 10.1016/j.tox.2003.10.011.
To clarify the alteration of androgenic and antiandrogenic activities by diesel engine conditions, we collected diesel exhaust particles (DEP) samples emitted from a diesel-engine truck under different conditions of engine loads and vehicle speeds, and DEP extract (DEPE) samples were prepared from each. The androgenic and antiandrogenic activities of the DEPE samples were examined using a prostate specific antigen (PSA) promoter-luciferase reporter gene assay in PC3/AR human prostate cancer cells. While all DEPE samples did not exhibit androgenic effects, the antiandrogenic effects were enhanced by higher engine load but not by higher vehicle speed. In this study, significant correlations between antiandrogenic and aryl hydrocarbon receptor (AhR) agonistic activities were demonstrated in PC3/AR cells by 16 polycyclic aromatic compounds and beta-naphthoflavone. Yeast two-hybrid assay and cytochrome P450 (CYP) 1A1 promoter-luciferase reporter gene assay showed that the antiandrogenic constituents acting as androgen receptor (AR) antagonists and AhR agonists were increased by only the higher engine load. In conclusion, the antiandrogenic effects of DEPE samples were enhanced by a higher engine load which resulted in DEPC samples with elevated AhR agonistic and AR antagonistic activities.
为了阐明柴油机工况对雄激素活性和抗雄激素活性的影响，我们收集了柴油发动机卡车在不同发动机负荷和车速条件下排放的柴油尾气颗粒（DEP）样本，并从每个样本中制备了DEP提取物（DEPE）样本。使用前列腺特异性抗原（PSA）启动子-荧光素酶报告基因检测法在PC3/AR人前列腺癌细胞中检测DEPE样本的雄激素活性和抗雄激素活性。虽然所有DEPE样本均未表现出雄激素效应，但抗雄激素效应在较高发动机负荷下增强，而在较高车速下未增强。在本研究中，16种多环芳烃化合物和β-萘黄酮在PC3/AR细胞中证明了抗雄激素活性与芳烃受体（AhR）激动活性之间存在显著相关性。酵母双杂交检测和细胞色素P450（CYP）1A1启动子-荧光素酶报告基因检测表明，仅在较高发动机负荷下，作为雄激素受体（AR）拮抗剂和AhR激动剂的抗雄激素成分增加。总之，较高的发动机负荷增强了DEPE样本的抗雄激素效应，导致DEPC样本的AhR激动活性和AR拮抗活性升高。
