Modulation of genotoxic and cytotoxic effects of aromatic amines in monolayers of rat hepatocytes

✍ Scribed by Jørn A. Holme; Erik J. Sønderland

• Publisher: Springer
• Year: 1984
• Tongue: English
• Weight: 1014 KB
• Volume: 1
• Category: Article
• ISSN: 0742-2091
• DOI: 10.1007/bf00125568

✦ Synopsis

The addition of pentachlorophenol or salicylamide all resulted in similar effects as ascorbate, through reduction of sulfation. Galactosamine, an inhibitor of glucuronidation, and the nucleophile GSH caused no or only minor effects of the activation of AAF, AF or N-OH-AAF as judged from the endpoints tested. These results are, consistent with an arylnitrenium ion, a sulfate ester or a free radical as the arylamine metabolite causing cellular DNA damage, whereas the sulfate ester or a radical intermediate may be responsible for the cytotoxic effects of N-OH-AAF.

Many chemical carcinogens must be metabolized to reactive electrophiles before they initiate tumor formation . The balance between activation and detoxification reactions is thus of primary importance in the carcinogenic process. Several attempts have been made to correlate carcinogenic potential with covalent macromolecular binding and with genotoxic effects of carcinogens. A good qualitative, but not always quantitative, relationship has been