Genotoxic potential of beta-carbolines: a review

The mutagenic and co-mutagenic properties of harman, norharman and of some of their pharmacologically important derivatives are reviewed. These compounds do not behave as true mutagens, but rather interact, directly or indirectly with DNA, leading to various consequences. This unusual behaviour is most probably related to the particular structure of the chemical nucleus common to all beta-carbolines which confers to the different derivatives the property to interact with various macromolecules and enzymatic systems. These interactions are compiled and discussed in this review. The alterations, by beta-carbolines, of some important enzymatic systems, e.g. cytochrome P-450, have been clearly demonstrated, yet many discrepancies and contradictions exist so that an interpretation of the results and the definition of some common mechanism appears premature. Since beta-carbolines are widely distributed in tissues and since they may modify and increase genotoxic and toxic consequences of other compounds, these interactions need to be clarified.