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 journalArticle

15 Citations (Scopus)

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

Fingerprint

Benzothiazoles
Aryl Hydrocarbon Receptors
Polycyclic Aromatic Hydrocarbons
tire
Tires
Biological Assay
PAH
hydrocarbon
Derivatives
Gene Expression
Aquatic Organisms
Poisons
Rubber
Cytochromes
Luciferases
Complex Mixtures
Toxicology
Bioassay
Fishes
Gene expression

Keywords

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

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Environmental Chemistry

Cite this

Identification of benzothiazole derivatives and polycyclic aromatic hydrocarbons as aryl hydrocarbon receptor agonists present in tire extracts. / He, Guochun; Zhao, Bin; Denison, Michael S.

In: Environmental Toxicology and Chemistry, Vol. 30, No. 8, 08.2011, p. 1915-1925.

Research output: Contribution to journalArticle

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