Bioactivation of 7-hydroxymethyl-12-methylbenz[a]anthracene by rat liver bile acid sulfotransferase I.
Bioactivation of 7-hydroxymethyl-12-methylbenz[a]anthracene by rat liver bile acid sulfotransferase I.
复制标题
大鼠肝胆汁酸磺基转移酶 I 对 7-羟甲基-12-甲基苯并[a]蒽的生物活性。
DOI：
10.1002/jbt.2570070407
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Barnes,S
中科院分区：
文献类型：
--
作者：
Falany,CN;Wheeler,J;Coward,L;Keehan,D;Falany,JL;Barnes,S
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.
