Triplet excited fluoroquinolones as mediators for thymine cyclobutane dimer formation in DNA.
A series of fluoroquinolones (FQs), including enoxacin (ENX), pefloxacin (PFX), norfloxacin (NFX), its N(4')-acetyl derivative (ANFX), ofloxacin (OFX), and rufloxacin (RFX) have been investigated to determine their potential as DNA photosensitizers via thymine cyclobutane dimer (T<>T) formation in DNA. At fluoroquinolone concentrations and light doses insufficient to produce direct single strand breaks, ENX, PFX, and NFX were able to produce T<>T dimers in DNA, revealed by enzymatic treatment with T4 endonuclease V. By contrast, ANFX, OFX, and RFX were inefficient in this assay. The absolute values of the triplet energies of ENX, PFX, NFX, ANFX, OFX, and RFX were estimated by means of laser flash photolysis, using flurbiprofen, 4-biphenylcarboxylic acid, and naproxen as energy acceptors. They were found to be 273, 269, 269, 265, 262, and 253 kJ/mol, respectively. Other triplet excited state properties of the FQs, including quantum yields and lifetimes, were also studied. All the results indicate that the threshold ET value required for a given compound to become a potential DNA photosensitizer via T<>T formation is in the range defined by the triplet energies of NFX and ANFX (265-269 kJ/mol). This provides the basis for an alert rule: any chemical (drugs, cosmetics, pesticides, etc.) with higher ET has to be considered with regard to its potential photogenotoxicity.
Lhiaubet-Vallet
Virginie
V
Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Valencia, Spain.
Cuquerella
M Consuelo
MC
Castell
Jose V
JV
Bosca
Francisco
F
Miranda
Miguel A
MA
D004247:DNA / Q000737:chemistry*; D019281:Dimerization; D024841:Fluoroquinolones / Q000737:chemistry*; D015394:Molecular Structure; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000737:chemistry; D011740:Pyrimidine Dimers / Q000737:chemistry*; D013057:Spectrum Analysis; D013941:Thymine / Q000737:chemistry*
D024841:Fluoroquinolones; D017319:Photosensitizing Agents; D011740:Pyrimidine Dimers; D004247:DNA; D013941:Thymine