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

Autor: Marilena Granzotto, Lucilla Dolzani, C. Monti-Bragadin, Cristina Lagatolla
Přispěvatelé: Lagatolla, Cristina, Dolzani, Lucilla, Granzotto, M, MONTI BRAGADIN, C.
Rok vydání: 1999
Předmět:
Zdroj: Teratogenesis, carcinogenesis, and mutagenesis. 18(5)
ISSN: 0270-3211
Popis: 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. Teratogenesis Carcinog. Mutagen. 18:239–248, 1998. © 1998 Wiley-Liss, Inc.
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