title: Activation of benzylic alcohols to mutagens by rat and human sulfotransferases expressed in Escherichia coli.
abstract: Human hydroxysteroid sulfotransferase, human phenol-sulfating form of phenol sulfotransferase, rat hydroxysteroid sulfotransferase a and rat phenol sulfotransferase IV were expressed in Escherichia coli. Cytosol preparations of transformed bacteria were used as activating systems in mutagenicity tests with Salmonella typhimurium TA98. All test compounds, 1-hydroxymethylpyrene, 2-hydroxymethylpyrene, 1-(1-pyrenyl)ethanol, 9-hydroxymethylanthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene and 4H-cyclopenta[def]chrysen-4-ol, were activated by both hydroxysteroid sulfotransferases investigated. However, 1-(1-pyrenyl)ethanol was 67-fold more efficiently activated by the human enzyme, whereas 7-hydroxymethyl-12-methylbenz[a]anthracene was 27-fold more efficiently activated by the rat enzyme. The phenol sulfotransferases showed relatively low activities with the benzylic alcohols investigated. The only exception was 4H-cyclopenta[def]chrysen-4-ol, which was activated efficiently by rat phenol sulfotransferase IV. We had previously tested the ability of rat and human hepatic cytosol preparations to activate the same compounds. The results of a statistical analysis suggest that the activities of human hydroxysteroid sulfotransferase, rat hydroxysteroid sulfotransferase a and phenol sulfotransferase IV can account for a substantial portion of the activation of benzylic alcohols in human, female rat and male rat liver, respectively.
authors.affiliation: Deutsches Institut für Ernährungsforschung, Potsdam-Rehbrücke, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Glatt
authors.forename: K
authors.initials: K
authors.lastname: Pauly
authors.forename: A
authors.initials: A
authors.lastname: Czich
authors.forename: J L
authors.initials: JL
authors.lastname: Falany
authors.forename: C N
authors.initials: CN
authors.lastname: Falany
mesh_terms: D000818:Animals; D001483:Base Sequence; D001592:Benzyl Alcohols / Q000378:metabolism* / Q000633:toxicity*; D001711:Biotransformation; D003001:Cloning, Molecular; D003600:Cytosol / Q000201:enzymology; D018076:DNA, Complementary / Q000096:biosynthesis; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism* / Q000633:toxicity*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D015238:Sulfotransferases / Q000378:metabolism*
chemical_list: D001592:Benzyl Alcohols; D018076:DNA, Complementary; D009153:Mutagens; D015238:Sulfotransferases