Genotoxic activity of 4,4',5'-trimethylazapsoralen on plasmid DNA.
The genotoxic activities of 8-methoxypsoralen (8-MOP) and 4,4',5'-trimethylazapsoralen (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 potential photochemotherapeutic activity. The mutagenic activity of mono- and bifunctional lesions caused by these compounds was evaluated both after UVA irradiation, which causes the formation of both kinds of lesions, and after a two-step irradiation procedure of the psoralen-plasmid DNA complex, which allowed monoadducts and interstrand crosslinks to be studied separately. Furthermore, we used a procedure that allowed us to evaluate both the mutagenic 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 potential. 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 mutagenic potentiality.
Lagatolla
C
C
Dipartimento di Scienze Biomediche, Università degli Studi, Trieste, Italy. lagatolla@fc.univ.trieste.it
Dolzani
L
L
Granzotto
M
M
Monti-Bragadin
C
C
D004247:DNA / Q000187:drug effects*; D011564:Furocoumarins / Q000633:toxicity*; D008730:Methoxsalen / Q000633:toxicity; D009154:Mutation; D010957:Plasmids; D014466:Ultraviolet Rays
D011564:Furocoumarins; C067366:4,4',5'-trimethylazapsoralen; D004247:DNA; D008730:Methoxsalen