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Isolation of the Glucuronic Acid Conjugate of N-Hydroxy-4-aminobiphenyl from Dog Urine and Its Mutagenic Activity¹

Departments of Pharmacology [J. L. R., W. L. H., T. R., H. M.] and Microbiology [W. E. S.], the University of Miami, School of Medicine, Miami, Florida 33152

The glucuronic acid conjugate of N-hydroxy-4-aminobiphenyl (NOH-4-ABP) has been isolated in relatively pure form from the urine of dogs given 4-aminobiphenyl, utilizing molecular size, ion exchange, adsorption, and partition chromatography. This conjugate is an active mutagen in Salmonella typhimurium strains TA1538 and TA98 but not in TA1535 or TA1537. NOH-4-ABP and 4-nitrosobiphenyl are also highly active in TA1538 and TA98 and inactive in TA1535 and TA1537. These observations support the concept that this conjugate is the water-soluble carrier that delivers the active metabolite to the bladder.

A substance of identical chromatographic and spectral properties to the conjugate isolated from dog urine has been synthesized in low yield by the direct condensation of NOH-4-ABP with glucuronic acid. This substance yields NOH-4-ABP on dilute acid hydrolysis. Sodium (N-4-biphenylhydroxylamino-ß-D-glucopyranosid) uronate, the N-O-C isomer, was also synthesized. It was found to have differing chromatographic and chemical properties to the natural conjugate. This evidence suggests that the urinary conjugate is the compound in which conjugation has occurred with the nitrogen atom of the hydroxylamine group rather than the oxygen atom.

¹ This investigation was supported by USPHS Grant CA05449 from the National Cancer Institute.

² To whom requests for reprints should be addressed.

Received 10/14/76. Accepted 3/14/77.