Oxidatively Generated Lesions as Internal Photosensitizers for Pyrimidine Dimerization in DNA

Autores de IIS La Fe

• Isabel Aparici Espert

  Autor

• Guillermo Garcia Lainez

  Autor

• Inmaculada Andreu Ros

  Autor

• Miguel Ángel Miranda Alonso

  Autor

• Virginie Lhiaubet Vallet

  Autor

Grupos

• Unidad Mixta de Investigación en Mecanismos moleculares de las Reacciones adversas de fármacos

Abstract

In this work, the attention is focused on UVA-photosensitized reactions triggered by a DNA chromophore-containing lesion, namely 5-formyluracil. This is a major oxidatively generated lesion that exhibits an enhanced light absorption in the UVB-UVA region. The mechanistic study combining photochemical and photobiological techniques shows that irradiation of S-formyluracil leads to a triplet excited state capable of sensitizing formation of cyclobutane pyrimidine dimers in DNA via a triplet-triplet energy transfer. This demonstrates for the first time that oxidatively generated DNA damage can behave as an intrinsic sensitizer and result in an important extension of the active fraction of the solar spectrum with photocarcinogenic potential. Overall, this raises the question of an aggravated photomutagenicity of the 5-formyluracil lesion.

Keywords

• 6-4 PHOTOPRODUCT; THYMINE; 5-FORMYLURACIL; DAMAGE; BASES