Glutathione conjugate formation in the detoxification of ultimate and proximate carcinogens of N-methyl-4-aminoazobenzene.

The presumed ultimate carcinogenic metabolite of the rat hepatocarcinogen N-methyl-4-aminoazobenzene (MAB), N-sulphonyloxy-MAB, was synthesized and reacted with glutathione (GSH) to yield the stable ring-substituted conjugates, 3-, 2'- and 4'-glutathion-S-yl-MAB (3-, 2'- and 4'-GSMAB) and the unstable methylene-substituted conjugate, N-(glutathion-S-methylene)-4-aminoazobenzene. Reaction of the model ultimate carcinogen, N-benzoyloxy-MAB, or the proximate carcinogen, N-hydroxy-MAB, with GSH also gave the same four conjugates. The ratio of ring-substitution relative to methylene conjugate formation increased with stronger leaving groups; i.e., ring-substitution increased in the order: N-hydroxy: N-benzoyloxy: N-sulphonyloxy. The ratio of 3-GSMAB to 2'- plus 4'-GSMAB was constant for all three MAB derivatives.