Novel Methodology for Predicting Photogenotoxic Risk of Pharmaceutical Substances Based on Reactive Oxygen Species (ROS) and DNA-Binding Assay
Abstract
Drug-induced phototoxic skin responses involves photoirritation, photoallergy, and photogenotoxicity. In the present study, we attempted to develop effective analytical tools to predict the photogenotoxic potential of pharmaceutical substances on the basis of their photobiological and DNA-binding properties. Photocleavage of plasmid DNA was assessed by capillary gel electrophoresis (CGE), and generation of reactive oxygen species (ROS) from photoirradiated photosensitizers was also assessed by spectrophotometrical determination. The affinity of drugs with DNA was determined by fluorescent titration or competitive binding assay using ethidium bromide. Structural transition from supercoiled form to open circular form of plasmid DNA were observed in the presence of nine irradiated-photosensitizers, however DNA damage by six phototoxic and five nonphototoxic drugs were negligible or weak even though some chemicals exhibited significant generation of ROS. DNA photocleavers tended to interact with DNA, binding constants of which were found to be less than 1 microM, whereas most nonphotogenotoxic chemicals failed to bind with DNA. The differences in DNA-binding properties might be attributed to a data discrepancy between ROS-generation and DNA photocleaving activity. The combination use of ROS assay and DNA-binding assay could be fast and reliable prediction for the photogenotoxic potential of a large number of drug candidates at the drug-discovery stage.
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ROS data might not always provide a reliable indication for the capacity of a chemical to participate in a photogenotoxic cascade.
“according to Onoue et al. [79], ROS data might not always provide a reliable indication for the capacity of a chemical to participant in a photogenotoxic cascade.”
From The Effect of Lycopene Preexposure on UV‐B‐Irradiated Human Keratinocytes (2016) · cites this paper as [79]
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“Previously, our group proposed three screening systems to predict the phototoxic risk of newly synthesized drug candidates, which include the reactive oxygen species (ROS) assay for predicting phototoxic potential (12–14), the capillary gel electrophoresis-based photocleavage assay (15), and the DNA-binding assay ( 16…”
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BackgroundCurrent and emerging new approach & methodologies for skin hazard assessment
Shin, S.-Y., & Lim, K. (2026) · Toxicological Research · doi:10.1007/s43188-026-00374-8
- Authors
- Onoue, S., Seto, Y., Oishi, A., & Yamada, S.
- Affiliations
- Shizuoka University (JP)
- Corresponding author
- Onoue, Satomi
- Venue
- Journal of Pharmaceutical Sciences
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 98
- Issue
- 10
- Pages
- 3647-3658
- ISSN
- 0022-3549 (ISSN-L)
- OpenAlex
- W2079072451
- Cited by
- 14
- References
- 31
- Citations by year
- 2026: 1 · 2020: 2 · 2018: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmaceutical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- 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
- Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Photochemistry and Electron Transfer Studies
- Keywords
- photogenotoxicity, reactive oxygen species, DNA binding affinity, photosensitizers, ethidium bromide binding, supercoiled DNA, drug discovery
- MeSH terms
- Circular Dichroism, DNA, DNA Damage, DNA, Superhelical, Ethidium, Light, Mutagens, Plasmids, Predictive Value of Tests, Spectrometry, Fluorescence, Photosensitizing Agents, Reactive Oxygen Species, Dermatitis, Phototoxic, Electrophoresis, Capillary, Drug-Related Side Effects and Adverse Reactions
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