title: Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines.
abstract: It has been well documented that β-carboline alkaloids, particularly the 9-methyl derivatives, are efficient photosensitizers. However, structure-activity relationships are missing and the photochemical mechanisms involved in the DNA photodamage still remain unknown. In the present work, we examined the capability of three 9-methyl-β-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 β-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 β-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 β-carbolines is responsible for 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.
authors.affiliation: Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Intendente Marino Km 8.2, CC 164 (B7130IWA), Chascomús, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Vignoni
authors.forename: Federico A O
authors.initials: FA
authors.lastname: Rasse-Suriani
authors.forename: Kathrin
authors.initials: K
authors.lastname: Butzbach
authors.forename: Rosa
authors.initials: R
authors.lastname: Erra-Balsells
authors.forename: Bernd
authors.initials: B
authors.lastname: Epe
authors.forename: Franco M
authors.initials: FM
authors.lastname: Cabrerizo
mesh_terms: D000818:Animals; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D019240:Corticoviridae / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004249:DNA Damage / Q000187:drug effects*; D004279:DNA, Viral / Q000235:genetics*; D008958:Models, Molecular; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D014466:Ultraviolet Rays
chemical_list: C529608:9-methyl-beta-carboline; D002243:Carbolines; D004279:DNA, Viral; D017319:Photosensitizing Agents; D004247:DNA; C427203:calf thymus DNA