Analysis of fluoroquinolone-mediated photosensitization of 2'-deoxyguanosine, calf thymus and cellular DNA: determination of type-I, type-II and triplet-triplet energy transfer mechanism contribution.
Fluoroquinolone (FQ) antibacterials are known to exhibit photosensitization properties leading to the formation of oxidative damage to DNA. In addition, photoexcited lomefloxacin (Lome) was recently shown to induce the formation of cyclobutane pyrimidine dimers via triplet-triplet energy transfer. The present study is aimed at gaining further insights into the photosensitization mechanisms of several FQ including enoxacin (Enox), Lome, norfloxacin (Norflo) and ofloxacin (Oflo). This was achieved by monitoring the formation of DNA base degradation products upon UVA-mediated photosensitization of 2'-deoxyguanosine, isolated and cellular DNA. Oflo and Norflo act mainly via a Type-II mechanism whereas Lome and, to a lesser extent, Enox behave more like Type-I photosensitizers. However, the extent of oxidative damage was found to be relatively low. In contrast, it was found that cyclobutane thymine dimers represent the major class of damage induced by Enox, Lome and Norflo within isolated and cellular DNA upon UVA irradiation. This striking observation confirms that FQ are able to promote efficient triplet energy transfer to DNA. The levels of photosensitized formation of strand breaks, alkali-labile sites and oxidative damage to cellular DNA, as measured by the comet assay, were confirmed to be rather low. Therefore, we propose that the phototoxic effects of FQ are mostly accounted for energy transfer mechanism rather than by Type-I or -II photosensitization processes.
Laboratoire des Lésions des Acides Nucléiques, Département de Recherche Fondamentale sur la Matière Condensée, Grenoble, France.
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S
Sauvaigo
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T
Douki
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F
Odin
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S
Caillat
J L
JL
Ravanat
J
J
Cadet
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002417:Cattle; D020552:Comet Assay; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects; D003849:Deoxyguanosine / Q000737:chemistry*; D004735:Energy Transfer; D024841:Fluoroquinolones; D017319:Photosensitizing Agents / Q000494:pharmacology*; D013950:Thymus Gland / Q000187:drug effects* / Q000528:radiation effects
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D017319:Photosensitizing Agents; D004247:DNA; D003849:Deoxyguanosine