Bioactivation of 7‐hydroxymethyl‐12‐ methyibenz[a]anthracene by rat liver bile acid sulfotransferase I

Academic Article


  • The bioactivation of 7‐hydroxy‐methyl‐12‐methylbenz[a]anthracene (HMBA) to an electrophilic sulfuric acid ester metabolite has been shown to be catalyzed by rat liver bile acid sulfotransferase I (BAST I). The sulfation and activation of HMBA by BAST I was determined by the ability of sulfated HMBA to form DNA ad‐ducts. The BAST I was also shown to react with rabbit anti‐human dehydroepiandrosterone sulfotransferase antisera and to represent a major form of hydroxysteroid/bile acid sulfotransferase in female rat liver cytosol. Higher levels of BAST I activity and immunoreactivity as well as HMBA‐DNA adduct formation were detected in female rat liver cytosol than in male rat liver cytosol. The bioactivation of HMBA by pure BAST I was dependent on the presence of 3′‐phosphoadenosine 5′‐phos‐phosulfate (PAPS) in the reaction and was inhibited by dehydroepiandrosterone, a physiological substrate for BAST I. Glutathione, a cellular nucleophile with important protective properties, decreased DNA adduct formation in the HMBA sulfation reaction in the absence of glutathione S‐transferase activity. These results indicate the usefulness of BAST I to investigate the sulfation and activation of HMBA and probably other hydroxy‐methylated polyaromatic hydrocarbons to electrophilic and mutagenic metabolites under defined reaction conditions. Copyright © 1992 Wiley‐Liss, Inc., A Wiley Company
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    Author List

  • Falany CN; Wheeler J; Coward L; Keehan D; Falany JL; Barnes S
  • Start Page

  • 241
  • End Page

  • 248
  • Volume

  • 7
  • Issue

  • 4