Molecular Responses to Photogenotoxic Stress Induced by the Antibiotic Lomefloxacin in Human Skin Cells: From DNA Damage to Apoptosis
Open accessAbstract
Photo-unstable chemicals sometimes behave as phototoxins in skin, inducing untoward clinical side-effects when exposed to sunlight. Some drugs, such as psoralens or fluoroquinolones, can damage genomic DNA, thus increasing the risk of photocarcinogenesis. Here, lomefloxacin, an antibiotic from the fluoroquinolone family known to be involved in skin tumor development in photoexposed mice, was studied using normal human skin cells in culture: fibroblasts, keratinocytes, and Caucasian melanocytes. When treated cells were exposed to simulated solar ultraviolet A (320-400 nm), lomefloxacin induced damage such as strand breaks and pyrimidine dimers in genomic DNA. Lomefloxacin also triggered various stress responses: heme-oxygenase-1 expression in fibroblasts, changes in p53 status as shown by the accumulation of p53 and p21 proteins or the induction of MDM2 and GADD45 genes, and stimulation of melanogenesis by increasing the tyrosinase activity in melanocytes. Lomefloxacin could also lead to apoptosis in keratinocytes exposed to ultraviolet A: caspase-3 was activated and FAS-L gene was induced. Moreover, keratinocytes were shown to be the most sensitive cell type to lomefloxacin phototoxic effects, in spite of the well-established effectiveness of their antioxidant equipment. These data show that the phototoxicity of a given drug can be driven by different mechanisms and that its biologic impact varies according to cell type.
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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 [150]
Cyclobutane pyrimidine dimers are detected by immunoassay in the DNA of fibroblasts, keratinocytes, and Caucasian melanocytes upon lomefloxacin photosensitization.
“CPDs were also detected by immunoassay in the DNA of fibroblasts, keratinocytes and Caucasian melanocytes upon lomefloxacin photosensitization (150).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [150]
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- Authors
- Marrot, L., Belaïdi, J. P., Jones, C., Perez, P., Meunier, J. R., Riou, L., & Sarasin, A.
- Affiliations
- L'Oréal (France) (FR)
- Corresponding author
- Marrot, Laurent
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2003-09
- Volume
- 121
- Issue
- 3
- Pages
- 596-606
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2032580699
- Cited by
- 70
- References
- 67
- Citations by year
- 2026: 2 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 1 · 2015: 2 · 2014: 3 · 2013: 4 · 2012: 7
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- lomefloxacin, phototoxicity, fluoroquinolones, DNA damage, UVA, apoptosis, keratinocytes, melanocytes, fibroblasts, heme oxygenase-1, p53, MDM2, GADD45, caspase-3, Fas ligand, melanogenesis, tyrosinase, pyrimidine dimers, photocarcinogenesis
- MeSH terms
- Anti-Infective Agents, Cells, Cultured, DNA Damage, Fibroblasts, Heme Oxygenase (Decyclizing), Humans, Melanocytes, Membrane Proteins, Skin, Skin Pigmentation, Ultraviolet Rays, Quinolones, Keratinocytes, Gene Expression, Tumor Suppressor Protein p53, Apoptosis, Photosensitizing Agents, Fluoroquinolones, Heme Oxygenase-1
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