Effects of harman and norharman on the metabolism and genotoxicity of 2-acetylaminofluorene in cultured rat hepatocytes

✍ Scribed by Jørn A. Holme; Erik Søderlund; Tore Aune

• Publisher: Springer
• Year: 1985
• Tongue: English
• Weight: 962 KB
• Volume: 1
• Category: Article
• ISSN: 0742-2091
• DOI: 10.1007/bf00120166

✦ Synopsis

Monolayers of rat hepatocytes metabolize 0.25 mM 2acetylaminofluorene (AA F) to various ether-extractable, watersoluble as well as covalently bound products. The major ether-extractable metabolite formed is 2-aminofluorene (AF), followed by 7-OH-AAF and 9-OH-AAF. Pretreatment of rats with the inducer Aroclor 1254 (PCB) increased the metabolism of AAF and caused an increased DATA repair synthesis in hepatocytes exposed to AAF or AF. With N-OH-AAF, a decreased genotoxic response in PCB-treated cells compared to control cells was seen. The addition of harman and norharman decreased the metabolism of AAF to ether-extractable metabolites, water-soluble metabolites and metabolites covalently bound to macromolecules. In contrast, the DNA-repair synthesis caused by the same concentrations of AAF was increased by harman. One explanation for this apparent discrepancy could be that the aromatic amines changed the metabolism of harman and norharman in such a way that these compounds were converted into genotoxic metabolites.