HEPATIC-METABOLISM OF N-HYDROXY-N-METHYL-4-AMINOAZOBENZENE AND OTHER N-HYDROXY ARYLAMINES TO REACTIVE SULFURIC-ACID ESTERS

  • 1 January 1976
    • journal article
    • research article
    • Vol. 36  (7) , 2350-2359
Abstract
Hepatic cytosols catalyzed a 3''-phosphoadenosine 5''-phosphosulfate (PAPS)-dependent O-sulfonation of the carcinogen N-hydroxy-N-methyl-4-aminoazobenzene (N-HO-MAB) and several other N-hydroxy arylamines. The presumed product from N-HO-MAB, N-methyl-4-aminoazobenzene-N-sulfate, reacted with added guanosine to yield N-(guanosin-8-yl)-N-methyl-4-aminoazobenzene, with methionine to form a sulfonium derivative that decomposed to yield 3-methylmecapto-N-methyl-4-aminoazobenzene and with ribosomal RNA to give to a bound derivative. N-Methyl-4-aminoazobenzene was converted to N-(guanosin-8-yl)-N-methyl-4-aminoazobenzene in concerted N-oxidation and O-sulfonation reactions conducted aerobically with a fortified 10,00 .times. g rat liver supernatant. In the absence of an added nucleophile, metabolically formed N-methyl-4-aminoazobenzene-N-sulfate(or the nitrenium ion from this unstable ester) was reduced by N-HO-MAB to form N-methyl-4-aminoazobenzene. N-HO-MAB was oxidized, probably through a nitrone intermediate, to yield products that included N-hydroxy-4-aminoazobenzene and formaldehyde. An analogous reaction was noted between N-benzoyloxy-N-methyl-4-aminoazobenzene and N-HO-MAB in the absence of cytosol and PAPS. Hepatic N-HO-MAB sulfotransferase activities were in the order; male rat > female rat, male rabbit, male guinea pig, male mouse > male hamster. Male rat kidney and small intestine cytosols had low activities. The other tissues studied had little or no activity. Hepatic sulfotransferase activities for N-HO-MAB and N-hydroxy-N-acetyl-2-aminofluorene displayed different pH optima and inhibitor and activator responses. The rates of PAPS-dependent rat liver cytosol-catalyzed esterification of N-hydroxy-N-ethyl-4-aminoazobenzene, N-hydroxy-4-aminoazobenzene and N-hydroxyl-1- and 2-naphthylamine were 20-50% of that for N-HO-MAB. Activities for trans-N-hydroxy-4-aminostilbene, N-hydroxy-2-aminofluorene, N-hydroxyaniline and N-hydroxy-N-methyl-N-benzylamine were not detected. No microsomal NADH-dependent reduction or NADPH-dependent oxidation or cytosolic transferase reactions for N-HO-MAB, except the above-described PAPS-dependent reaction, were detected in rat liver.