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. Th ese compounds do not behave as true mutagens, but rather interact, dir ectly or indirectly with DNA, leading to various consequences. This un usual behaviour is most probably related to the particular structure o f the chemical nucleus common to all beta-carbolines which confers to the different derivatives the property to interact with various macrom olecules and enzymatic systems. These interactions are compiled and di scussed in this review. The alterations, by beta-carbolines, of some i mportant enzymatic systems, e.g. cytochrome P-450, have been clearly d emonstrated, yet many discrepancies and contradictions exist so that a n interpretation of the results and the definition of some common mech anism 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 clarifi ed.