N-GLUCURONIDATION OF N-HYDROXY AROMATIC-AMINES - MECHANISM FOR THEIR TRANSPORT AND BLADDER-SPECIFIC CARCINOGENICITY

Glucuronide conjugates of carcinogenic N-hydroxy metabolites of the primary aromatic amines, 4-aminobiphenyl (4-ABP), 2-naphthylamine (2-NA), and 1-naphthylamine (1-NA) were isolated from the urine of dogs administered the respective primary amine and from the in vitro incubation of N-hydroxy metabolites with uridine-5′-disphosphoglucuronic acid-fortified dog liver microsomes. The urinary and microsomal conjugates were purified by several sequential chromatographic procedures, including Sephadex G-15, Amberlite XAD-2, and cellulose CF-11 chromatography for microsomal conjugates and Sephadex G-10, DEAE, and Amberlite XAD-2 chromatography for urinary conjugates. The infrared spectra of purified urinary and microsomal conjugates of these three N-hydroxy aromatic amines were identical to spectra of authentic NC glucuronides prepared by two different synthetic procedures. The urinary and microsomal conjugates comigrated with synthetic NC glucuronides in two solvent systems. These observations in conjunction with previous studies provide evidence that NC glucuronidation represents a general metabolic reaction of carcinogenic N-hydroxy aromatic amines which provides the means of transport of these compounds to their site of action in the bladder. © 1979.