In vitro DNA binding of 2-amino-3-methylimidazo(4,5-f)[5-3H]quinoline (IQ) is modulated by sulfotransferase and sulfate levels.
DNA binding in vitro was measured with 2-amino-3- methylimidazo(4,5-f)[5-3H]quinoline (3H-IQ) in the presence of S9 and microsomes from Wistar rat liver. DNA binding of 3H-IQ was catalyzed by both microsomes and S9 and was increased 5-fold in Aroclor (PCB)-pretreated animals. DNA binding was reduced by the specific inhibitor of sulfotransferase 2,6-dichloro-4-nitrophenol and slightly increased by 3'-phosphoadenosine 5'-phosphosulfate. The incubation of IQ in media with increasing concentrations of sulfate produced a modest dose-dependent increase in DNA binding. Liver S9 obtained from rats which had been administered 1% sulfite in drinking water catalyzed a higher binding of IQ to DNA, and this effect was inhibited by pentachlorophenol. The data demonstrate that sulfotransferase has a role in the activation of IQ and that variations in the activity of this enzyme induced by dietary changes may vary the genotoxic activity of IQ.
Lodovici
M
M
Department of Pharmacology, University of Florence, Italy.
Grassi
M
M
Dolara
P
P
D000818:Animals; D001711:Biotransformation; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism*; D051381:Rats; D013431:Sulfates / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism
D009153:Mutagens; D011804:Quinolines; D013431:Sulfates; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D004247:DNA; D015238:Sulfotransferases