Lagatolla C, Dolzani L, Granzotto M, Monti-Bragadin C
Dipartimento di Scienze Biomediche, Università degli Studi, Trieste, Italy.
Teratog Carcinog Mutagen. 1998;18(5):239-48.
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.
已对8-甲氧基补骨脂素（8-MOP）和4,4',5'-三甲基氮杂补骨脂素（4,4',5'-TMAP）对质粒DNA的遗传毒性活性进行了比较。在先前的一项研究中，补骨脂素类似物的甲基衍生物4,4',5'-TMAP已显示出潜在的光化学治疗活性。在紫外线A（UVA）照射后（会导致两种损伤的形成）以及在对补骨脂素-质粒DNA复合物进行两步照射程序后（可分别研究单加合物和链间交联），对这些化合物引起的单功能和双功能损伤的诱变活性进行了评估。此外，我们采用了一种程序来评估这两种化合物的诱变活性和重组活性。结果表明，8-MOP和4,4',5'-TMAP之间最重要的区别在于它们与DNA的光反应模式，而非诱变潜力。事实上，在所有实验程序中，4,4',5'-TMAP产生链间交联的能力均低于8-MOP。然而，当达到相当的毒性水平时，这两种化合物表现出相同的诱变潜力。
