ACTIVATION OF BENZYLIC ALCOHOLS TO MUTAGENS BY RAT AND HUMAN SULFOTRANSFERASES EXPRESSED IN ESCHERICHIA-COLI

Human hydroxysteroid sulfotransferase, human phenol-sulfating form of phenol sulfotransferase, rat hydroxysteroid sulfotransferase a and rat phenol sulfotransferase IV were expressed in Escherichia coli. Cytoso l preparations of transformed bacteria were used as activating systems in mutagenicity tests with Salmonella typhimurium TA98. All test comp ounds, 1-hydroxmyethylpyrene, 2-hydroxymethylpyrene, 1-(1-pyrenyl)etha nol, 9-hydroxymethylanthracene, 7-hydroxymethyl-12-methylbenz[a]anthra cene and 4H-cyclopenta[def]chrysen-4-ol, were activated by both hydrox ysteroid 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 rela tively low activities with the benzylic alcohols investigated. The onl y exception was 4H-cyclopenta[def]chrysen-4-ol, which was activated ef ficiently 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 hydroxys teroid sulfotransferase a and phenol sulfotransferase IV can account f or a substantial portion of the activation of benzylic alcohols in hum an, female rat and male rat liver, respectively.