Benzo[ a]pyrene Induction of Glutathione S-Transferases: An Activity-Based Protein Profiling Investigation

Chem Res Toxicol. 2019 Jun 17;32(6):1259-1267. doi: 10.1021/acs.chemrestox.9b00069. Epub 2019 Apr 12.


Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated from combustion of carbon-based matter. Upon ingestion, these molecules can be bioactivated by cytochrome P450 monooxygenases to oxidized toxic metabolites. Some of these metabolites are potent carcinogens that can form irreversible adducts with DNA and other biological macromolecules. Conjugative enzymes, such as glutathione S-transferases or UDP-glucuronosyltransferases, are responsible for the detoxification and/or facilitate the elimination of these carcinogens. While responses to PAH exposures have been extensively studied for the bioactivating cytochrome P450 enzymes, much less is known regarding the response of glutathione S-transferases in mammalian systems. In this study, we investigated the expression and activity responses of murine hepatic glutathione S-transferases to benzo[ a]pyrene exposure using global proteomics and activity-based protein profiling for chemoproteomics, respectively. Using this approach, we identified several enzymes exhibiting increased activity including GSTA2, M1, M2, M4, M6, and P1. The activity of one GST enzyme, GSTA4, was found to be downregulated with increasing B[ a]P dose. Activity responses of several of these enzymes were identified as being expression-independent when comparing global and activity-based data sets, possibly alluding to as of yet unknown regulatory post-translational mechanisms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Benzo(a)pyrene / chemistry
  • Benzo(a)pyrene / pharmacology*
  • Enzyme Induction / drug effects
  • Female
  • Glutathione Transferase / metabolism*
  • Liver / drug effects
  • Liver / metabolism
  • Mice
  • Mice, Inbred Strains
  • Molecular Probes / chemistry
  • Molecular Structure
  • Proteomics
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism


  • Molecular Probes
  • RNA, Messenger
  • Benzo(a)pyrene
  • Glutathione Transferase