Mechanisms of DNA damage by photoexcited 9-methyl-b-carbolines

MARIANA VIGNONI; FEDERICO A. O. RASSE-SURIANI; KATHRIN BUTZBACH; ROSA ERRA-BALSELLS; BERND EPE*; FRANCO M. CABRERIZO*

ORGANIC & BIOMOLECULAR CHEMISTRY

ROYAL SOC CHEMISTRY

Lugar: CAMBRIDGE; Año: 2013 vol. 11 p. 5300 - 5309

1477-0520

It has been well documented that b-carboline alkaloids, particularly the 9-methyl derivatives, are efficient photosensitizers. However, structure-activity relations are missing and the photochemical mechanisms involved in the DNA photodamage still remains unknown. In the present work, we examined the capability of three 9-methyl-b-carbolines (9-methyl-norharmane, 9-methyl-harmane and 9-methyl-harmine) to induce DNA damage upon UVA excitation at physiological pH. The type and extent of the damage was analyzed together with the photophysical and binding properties of the b-carboline derivatives investigated. The results indicate that even at neutral pH most of the DNA damage is generated from the protonated form of the excited b-carbolines in a type-I reaction. Oxidized purine residues are produced in high excess over oxidized pyrimidines, single-strand breaks and sites of base loss. In addition, the excited neutral form of the b-carbolines is responsible for a significant generation of cyclobutane pyrimidine dimers (CPDs) by triplet-triplet-energy transfer. In the case of 9-methyl-norharmane, the yield of CPDs is increased in D2O, probably due to less rapid protonation in the deuterated solvent.