Sulfation of hydroxylamines and hydroxamic acids in liver cytosol from male and female rats and purified aryl sulfotransferase IV.

Sulfation activity towards hydroxamic acids and hydroxylamines was determined in liver cytosols for juvenile and adult males and female rats, as well as in purified rat liver aryl sulfotransferase IV preparations. Sulfation activity towards the hydroxamic acids N-hydroxy-2-acetylaminofluorene, N-hydroxy-2-acetylaminophenanthrene, N-hydroxy-4-acetylaminobiphenyl, N-hydroxy-4'-fluoro-4-acetylaminobiphenyl, N-hydroxy-2-acetylamino-5-phenylpyridine, was higher in cytosols derived from adult males (two or three times) than in those from adult females and juveniles (both sexes). N-Hydroxy-2-acetylamino-3-methyl-5-phenylpyridine (N-OH-2AAMPP), however, was poorly sulfated by any of the cytosols. Sulfation activity towards the hydroxylamines N-hydroxy-2-aminofluorene, N-hydroxy-2-aminophenanthrene, N-hydroxy-4-aminobiphenyl, N-hydroxy-4'-fluoro-4-aminobiphenyl was much lower. N-Hydroxy-2-amino-5-phenylpyridine (N-OH-2APP), however, was sulfated much better than the other hydroxylamines. No higher sulfation activity in adult male cytosols for hydroxylamines was found, except for N-OH-2APP and N-hydroxy-2-amino-3-methyl-5-phenylpyridine (N-OH-2AMPP). Purified aryl sulfotransferase IV (AST IV) converted all hydroxamic acids; N-OH-2AAMPP was a poor substrate. Of the hydroxylamines only N-OH-2APP and N-OH-2AMPP were conjugated. These results suggest that hydroxylamines and hydroxamic acids are converted by different sulfotransferases in the rat in vivo. They also indicate that AST IV may be the major enzyme responsible for sulfation of a variety of aromatic hydroxamic acids in the male rat liver. The results presented here are discussed in relation to the carcinogenic effects of some of these compounds.