Structural basis of the genotoxicity of nitrosatable phenols and derivatives present in smoked food products

Abstract

The CASE methodology for studying structure-activity relationships has been applied to investigating the basis of the genotoxicity of phenols and derivatives following exposure to nitrous acid. The structural feature identified include availability of positions para or ortho to the hydroxyl groups, that one meta position must remain unoccupied and one ortho or para position must be unsubmitted as well. The analyses reveald that genotoxicity is dependent upon the ease of formation of the active phenyldiazonium intermediate and is influenced only secondarily by the nature of the genotoxicant or its ease of entry into the cell. With this data base, CASE predicts the genotoxicity, following nitrosation, of a number agents, including serotonin, acetaminophen, and of some naturally-occuring pesticides present in edible plants.