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Cited by 9DNA Repair MechanismsCarcinogens and Genotoxicity AssessmentBioactive Compounds and Antitumor Agents

Photosensitization induced by the antibacterial fluoroquinolone Rufloxacin leads to mutagenesis in yeast

Serrentino, Maria-Elisabetta, Catalfo, Alfio, Angelin, Anne-Reynaud, de Guidi, Guido, Sage, Evelyne·2010·Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
DOI 10.1016/j.mrfmmm.2010.07.011
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Abstract

Rufloxacin (RFX) is an antibacterial fluoroquinolone that exhibits UVA photosensitization properties. Photosensitization reactions lead to the formation of oxidative damage, mainly via singlet oxygen. Here we explore the phototoxic and photomutagenic potency of RFX using a panel of yeast (Saccharomyces cerevisiae) mutants affected in different DNA repair pathways. Yeast mutants provide a sensitive tool to identify the photodamage and the DNA repair pathways that cope with it. Cell viability test at increasing dose of UVA shows that both the DNA repair deficient and wild type cells are equally sensitive to RFX-induced photosensitization, demonstrating that phototoxic effect is not due to DNA injury. Photomutagenicity of RFX is evaluated by measuring the frequency of forward Can(R) mutations. The mutation induction is low in wild type cells. A high increase in mutation frequency is observed in strains affected in Ogg1 gene, compared to wild type and other base excision repair deficient strains. The mutation spectrum photomediated by RFX in wild type cells reveals a bias in favour of GC>TA transversions, whereas transition 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, leading to mutagenesis. We also explore the role played by DNA mismatch repair, translesion synthesis and post-replication repair in the prevention of mutagenic effects due to RFX exposure. In addition, we show that most of RFX photodegradation products are not mutagenic. This study defines the phototoxic and photomutagenic properties of antibacterial RFX and point out possible unwanted side effects in skin under sunlight.

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Crossref · 10.1016/j.mrfmmm.2010.07.011

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  • Enhanced frequency of GC>TA transversions in yeast after fluoroquinolone photosensitization supports predominant formation of 8-oxoGua.

    “Further support for the predominant formation of 8-oxoGua among the DNA damage induced by UVA-excited rufloxacin UVA was provided by the enhanced frequency of GC>TA transversions in yeast after fluoroquinolone photosensitization (181).”

    From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [181]

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Authors
Serrentino, M.-E., Catalfo, A., Angelin, A.-R., de Guidi, G., & Sage, E.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • University of Catania (IT)
ORCID
Catalfo, Alfio
Venue
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Publisher
Elsevier BV
Published
2010-10
Volume
692
Issue
1-2
Pages
34-41
ISSN
  • 0027-5107 (ISSN-L)
  • 1386-1964
DOI
10.1016/j.mrfmmm.2010.07.011
OpenAlex
W1978963364
Cited by
9
References
46
Citations by year
2021: 1 · 2016: 1 · 2014: 2 · 2012: 2
FWCI
0.65
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Mutation research. Fundamental and molecular mechanisms of mutagenesis (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Centre National de la Recherche Scientifique
  • Institut Curie
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
Keywords
rufloxacin, fluoroquinolones, photosensitization, photomutagenesis, singlet oxygen, DNA repair, OGG1, base excision repair, 8-oxo-7,8-dihydroguanine, mutation spectrum, DNA mismatch repair, translesion synthesis, postreplication repair, photodegradation products
MeSH terms
Anti-Bacterial Agents, DNA Repair, Guanine, Mutagens, Photosensitivity Disorders, Saccharomyces cerevisiae, Ultraviolet Rays, Mutagenesis, Fluoroquinolones

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