Antiandrogenic activity of extracts of diesel exhaust particles emitted from diesel-engine truck under different engine loads and speeds

Kazumasa Okamura, Ryoichi Kizu, Akira Toriba, Tsuyoshi Murahashi, Atsushi Mizokami, Kerry L. Burnstein, Carolyn M. Klinge, Kazuichi Hayakawa

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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 β-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.

Original languageEnglish (US)
Pages (from-to)243-254
Number of pages12
JournalToxicology
Volume195
Issue number2-3
DOIs
StatePublished - Feb 15 2004

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Keywords

  • Androgen receptor antagonists
  • Antiandrogenic activity
  • Aryl hydrocarbon receptor agonists
  • Diesel exhaust particles
  • Engine load

ASJC Scopus subject areas

  • Toxicology

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