Rat Mammary Gland Carcinogenesis After Local Injection of N-Hydroxy-N-Acyl-2-Aminofluorenes: Relationship to Metabolic Activation

摘要

A single local injection of 2.5 umoles of N-hydroxy-N-formyl-2-aminofluorene (N-hydroxy-FAF), N-hydroxy-N-acetyl-2-aminofluorene (N-hydroxy-AAF), or N-hydroxy-N-propionyl-2-aminofluorene (N-hydroxy-PAF) to each of the six left mammary glands of female Sprague-Dawley derived CD rats gave a mammary tumor incidence, after 12 months, of 53% for N-hydroxy-AAF (42% adenocarcinoma, 11% fibroadenoma), 41% for N-hydroxy-FAF (8% adenocarcinoma, 11% sarcoma, 22% fibroadenoma), and 33% for N-hydroxy-PAF (11% adenocarcinoma, 22% fibroadenoma). Assays that tested the mutagenic potential of the arylhydroxamic acids in Salmonella typhimurium TA-1538 with either mammary gland cytosol or microsomes demonstrated the order of mutagenicity to be N-hydroxy-FAF>>N-hydroxy-PAF. A similar order of mutagenicity was demonstrated without an external metabolic activation system.