Identification of benzothiazole derivatives and polycyclic aromatic hydrocarbons as aryl hydrocarbon receptor agonists present in tire extracts

Guochun He, Bin Zhao, Michael S. Denison

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Leachate from rubber tire material contains a complex mixture of chemicals previously shown to produce toxic and biological effects in aquatic organisms. The ability of these leachates to induce Ah receptor (AhR)-dependent cytochrome P4501A1 expression in fish indicated the presence of AhR active chemicals, but the responsible chemicals and their direct interaction with the AhR signaling pathway were not examined. Using a combination of AhR-based bioassays, we have demonstrated the ability of tire extract to stimulate both AhR DNA binding and AhR-dependent gene expression and confirmed that the responsible chemicals were metabolically labile. The application of CALUX (chemical-activated luciferase gene expression) cell bioassay-driven toxicant identification evaluation not only revealed that tire extract contained a variety of known AhR-active polycyclic aromatic hydrocarbons but also identified 2-methylthiobenzothiazole and 2-mercaptobenzothiazole as AhR agonists. Analysis of a structurally diverse series of benzothiazoles identified many that could directly stimulate AhR DNA binding and transiently activate the AhR signaling pathway and identified benzothiazoles as a new class of AhR agonists. In addition to these compounds, the relatively high AhR agonist activity of a large number of fractions strongly suggests that tire extract contains a large number of physiochemically diverse AhR agonists whose identities and toxicological/biological significances are unknown.

Original languageEnglish (US)
Pages (from-to)1915-1925
Number of pages11
JournalEnvironmental Toxicology and Chemistry
Volume30
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • Ah receptor
  • Benzothiazoles
  • CALUX
  • Tires
  • Toxicant identification evaluation

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Environmental Chemistry

Fingerprint

Dive into the research topics of 'Identification of benzothiazole derivatives and polycyclic aromatic hydrocarbons as aryl hydrocarbon receptor agonists present in tire extracts'. Together they form a unique fingerprint.

Cite this