J. Miller, Carole S. Wyatt, E. Miller
Nov 1, 1961
Citations
1
Influential Citations
122
Citations
Quality indicators
Journal
Cancer Research
Abstract
Summary N -Hydroxy-4-acetylaminobiphenyl has been identified as a urinary metabolite of the carcinogens 4-acetylaminobiphenyl and 4-aminobiphenyl in the rat. 4-Acetylaminobiphenyl, but not 4-aminobiphenyl, yielded the same metabolite in the dog. The N -hydroxy metabolite was excreted as a conjugate which was easily cleaved by a bacterial β-glucuronidase preparation but not by Takadiastase. The identity of the metabolic N -hydroxy-4-acetylaminobiphenyl was established by its isolation in crystalline form and comparison with the synthetic compound. In opposition to the situation previously observed with 2-acetylaminofluorene in the rat, N -hydroxy-4-acetylaminobiphenyl was found in gradually decreasing amounts in the urine as the feeding of 4-acetylaminobiphenyl to rats progressed over several months. Upon oral administration to adult female rats N -hydroxy-4-acetylaminobiphenyl was as active a mammary carcinogen as 4-acetylaminobiphenyl and also induced more ear-duct carcinomas and forestomach papillomas than the parent amide. Upon repeated intraperitoneal injection into young female rats N -hydroxy-4-acetylaminobiphenyl was more active than 4-acetylaminobiphenyl as a mammary carcinogen. Dietary 3-methylcholanthrene had no marked effect on the N -hydroxylation of 4-acetylaminobiphenyl or on the carcinogenicity of this amide and its N -hydroxy metabolite toward the mammary gland. N -Hydroxy-4-acetylaminobiphenyl appears to be one of the proximate agents in carcinogenesis by 4-acetylaminobiphenyl in the rat.