Activation of benzylic alcohols to mutagens by human hepatic sulphotransferases.
Four primary and five secondary benzylic alcohols derived from polycyclic aromatic hydrocarbons were tested for mutagenicity in Salmonella typhimurium TA98 in the presence of 3'-phosphoadenosine-5'-phosphosulphate, the cofactor for sulphotransferases, and varying amounts of hepatic cytosol from three or four different human subjects, a 3-year-old child, an adult female, an adult male and one unknown. All compounds except one, 4H-cyclopenta[def]phenanthren-4-ol, were activated to mutagens. The interindividual variation in the activities was at most 3-fold and the individual activities towards the different substrates were correlated with each other. The same compounds had previously been tested in the presence of hepatic cytosol from rats and all compounds activated in one species were also activated in the other species. However, there were marked quantitative differences, which were further complicated by the observation of a substantial sex difference in the rat. Male and female rat liver cytosol showed higher sulphotransferase activities towards 1-hydroxymethylpyrene, 9-hydroxymethylanthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene and 4H-cyclopenta[def]chrysen-4-ol than human liver cytosol. The largest difference in activity was seen with 7-hydroxymethyl-12-methylbenz[a]anthracene, reaching a factor of approximately 100 between human and female rat. However, with other benzylic alcohols, the activity in human liver cytosol was in the range of that found in the less active sex of rat (3-hydroxy-3,4-dihydrocyclopenta[cd]pyrene, 2-hydroxymethylpyrene) or the more active sex of rat [1-(1-pyrenyl)ethanol].(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Toxicology, Deutsches Institut für Ernährungsforschung, Potsdam-Rehbrücke, Germany.
H
H
Glatt
A
A
Seidel
R G
RG
Harvey
M W
MW
Coughtrie
D000818:Animals; D001592:Benzyl Alcohols / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship; D015238:Sulfotransferases / Q000494:pharmacology*
D001592:Benzyl Alcohols; D009153:Mutagens; D015238:Sulfotransferases