Rufloxacin (RFX) is an antibacterial fluoroquinolone that exhibits UVA photosensitization properties.Photosensitization reactions lead to the formation of oxidative damage, mainly via singlet oxygen. Herewe explore the phototoxic and photomutagenic potency of RFX using a panel of yeast (Saccharomycescerevisiae) mutants affected in different DNA repair pathways. Yeast mutants provide a sensitive tool toidentify the photodamage and the DNA repair pathways that cope with it. Cell viability test at increasingdose of UVA shows that both the DNA repair deficient and wild type cells are equally sensitive toRFX-induced photosensitization, demonstrating that phototoxic effect is not due to DNA injury. Photomutagenicityof RFX is evaluated by measuring the frequency of forward CanR mutations. The mutationinduction is low in wild type cells. A high increase in mutation frequency is observed in strains affectedin Ogg1 gene, compared to wild type and other base excision repair deficient strains. The mutation spectrumphotomediated by RFX in wild type cells reveals a bias in favour of GC> TA transversions, whereastransition and frameshift mutations are less represented. Altogether data demonstrates that 8-oxo-7,8-dihydroguanine (8-oxoGua) is by far the major DNA damage produced by RFX photosensitization, leadingto mutagenesis.Wealso explore the role played by DNA mismatch repair, translesion synthesis and postreplicationrepair in the prevention of mutagenic effects due to RFX exposure. In addition, we show thatmost of RFX photodegradation products are not mutagenic. This study defines the phototoxic and photomutagenicproperties of antibacterial RFX and point out possible unwanted side effects in skin undersunlight.
|Titolo:||Photosensitization induced by the antibacterial fluoroquinolone Rufloxacin leads to mutagenesis in yeast|
|Data di pubblicazione:||2010|
|Citazione:||Photosensitization induced by the antibacterial fluoroquinolone Rufloxacin leads to mutagenesis in yeast / DE GUIDI G; MARIA-ELISABETTA SERRENTINO; ALFIO CATALFO; ANNE-REYNAUD ANGELIN; EVELYNE SAGE. - In: MUTATION RESEARCH. - ISSN 0027-5107. - 692(2010), pp. 34-41.|
|Appare nelle tipologie:||1.1 Articolo in rivista|