Formation of 3-(glutathion-S-YL)-N-methyl-4-aminoazobenzene and inhibition of aminoazo dye-nucleic acid binding in vitro by reaction of glutathione with metabolically-generated N-methyl-4-aminoazobenzene-N-sulfate.
The reaction of glutathione (GSH) with metabolically-formed N-methyl-4-aminoazobenzene-N-sulfate (MAB-N-sulfate), a presumed ultimate carcinogenic metabolite of N,N-dimethyl-4-aminoazobenzene (DAB), was investigated using a hepatic sulfotransferase incubation mixture containing GSH and the proximate carcinogen, N-hydroxy-N-methyl-4-aminoazobenzene (N-HO-MAB). Under these conditions, 6--16% of the MAB-N-sulfate formed could be trapped as an aminoazo dye-GSH adduct. Upon subsequent purification, the adduct was shown to be chromatographically and spectrally identical to 3-(glutathion-S-yl)-N-methyl-4-aminoazobenzene (3-GS-MAB), a known biliary metabolite of DAB and a product of the reaction of the synthetic ultimate carcinogen, N-benzoyloxy-N-methyl-4-aminoazobenzene(N-BzO-MAB), with GSH. Neither 2'- nor 4'-GS-MAB, both products of the latter reaction, were detected in the sulfotransferase incubation mixture. GSH-S-transferases did not appear to be involved in the reaction of MAB-N-sulfate of N-BzO-MAB with GSH. The addition of triethyltin, a potent GSH-S-transferase inhibitor, had no effect on the yield of 3-GS-MAB in (N-HO-MAB sulfotransferase)-GSH incubations; and the addition of cytosol or purified GSH transferases A and B to a (N-BzO-MAB)-GSH reaction mixture did not increase the amount of 3-GS-MAB formed.
D000818:Animals; D001391:Azo Compounds / Q000378:metabolism*; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D004396:Coloring Agents / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009696:Nucleic Acids / Q000378:metabolism*; D051381:Rats; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives / Q000378:metabolism*
D001391:Azo Compounds; D004396:Coloring Agents; D009696:Nucleic Acids; D010128:p-Aminoazobenzene; C026701:N-methyl-4-aminoazobenzene-N-sulfate; C026707:3-(glutathion-S-yl)-N-methyl-4-aminoazobenzene; D005982:Glutathione Transferase; D005978:Glutathione