The Phototumorigenic Fluoroquinolone Lomefloxacin Photosensitizes Pyrimidine Dimer Formation in Human Keratinocytes In Vitro
Abstract
The fluoroquinolone antibiotic lomefloxacin is phototoxic, photogenotoxic, photomutagenic and photosensitizes tu‐morigenesis in mouse skin. We have used T4 endonucle‐ase V to demonstrate that lomefloxacin photosensitizes pyrimidine dimer formation in a human keratinocyte line (HaCaT). A possible mechanism for this effect would be triplet‐triplet energy transfer. However, there is indirect evidence that the lomefloxacin triplet yield is very low, making this reaction less likely. The finding that lomefloxacin photosensitizes production of highly mutagenic pyrimidine dimers correlates with its ability to initiate skin tumor formation in mice. Until the potential of other fluoroquinolones to photosensitize dimer formation is explored it may be unadvisable to prescribe these antibiotics to patients with defective DNA repair capacity (e.g. xeroderma pigmentosum).
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UVA-excited lomefloxacin generates cyclobutane pyrimidine dimers in human keratinocytes, detected as T4 endonuclease V-sensitive sites.
“Thus, UVA-excited lomefloxacin has been found to generate in human keratinocytes CPDs that were revealed as T4 endonuclease V-sensitive sites (149).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [149]
UVA-sensitized formation of cyclobutane pyrimidine dimers by fluoroquinolones occurs in the DNA of isolated cells and mouse skin.
“Several examples of UVA-sensitized formation of CPDs by fluoroquinolones in the DNA of isolated cells (93,149,150) and mouse skin (151) are available.”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [149]
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Self-citation
- Authors
- Traynor, N. J., & Gibbs, N. K.
- Affiliations
- University of Dundee (GB)
- Corresponding author
- Gibbs, Neil K.
- ORCID
- Gibbs, Neil K.
- Venue
- Photochemistry and Photobiology
- Publisher
- Wiley
- Published
- 1999-12
- Volume
- 70
- Issue
- 6
- Pages
- 957-959
- ISSN
- 0031-8655 (ISSN-L)
- 1751-1097
- OpenAlex
- W1967532615
- Cited by
- 26
- References
- 20
- Citations by year
- 2021: 2 · 2020: 1 · 2015: 1 · 2014: 3 · 2013: 1 · 2012: 1
- FWCI
- 0.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Photochemistry and Photobiology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Funders
- Tenovus
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Keywords
- lomefloxacin, fluoroquinolones, phototoxicity, photomutagenesis, photosensitization, keratinocytes, triplet-triplet energy transfer, T4 endonuclease V, skin carcinogenesis, xeroderma pigmentosum, DNA repair deficiency
- MeSH terms
- Anti-Infective Agents, Cell Line, Transformed, DNA Damage, Humans, Pyrimidine Dimers, Quinolones, Keratinocytes, Photosensitizing Agents, Fluoroquinolones
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