Genotoxic activity of 4,4 ',5 '-trimethylazapsoralen on plasmid DNA

The genotoxic activities of 8-methoxypsoralen (8-MOP) and 4,4',5'-trimethyl azapsoralen (4,4',5'-TMAP) on plasmid DNA have been compared. In a previous work, 4,4',5'-TMAP, a methyl derivative of a psoralen isoster, had shown p otential photochemotherapeutic activity. The mutagenic activity of mono- an d bifunctional lesions caused by these compounds was evaluated both after U VA irradiation, which causes the formation of both kinds of lesions, and af ter a two-step irradiation procedure of the psoralen-plasmid DNA complex, w hich allowed monoadducts and interstrand crosslinks to be studied separatel y. Furthermore, we used a procedure that allowed us to evaluate both the mu tagenic and recombinogenic activity of the two compounds. Results indicate that the most important difference between 8-MOP and 4,4',5'-TMAP consists in their mode of photoreaction with DNA rather than in their mutagenic pote ntial. In fact, in all of the experimental procedures, 4,4',5'-TMAP shows a lower ability than 8-MOP to generate interstrand crosslinks. However, when comparable toxicity levels are reached, the two compounds show the same mu tagenic potentiality. (C) 1998 Wiley-Liss,Inc.