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Journal of Radiation Research Mar 2015Histone H2AX is a minor component of nuclear histone H2A. The phosphorylation of histone H2AX at Ser 139, termed γ-H2AX, was originally identified as an early event... (Review)
Review
Histone H2AX is a minor component of nuclear histone H2A. The phosphorylation of histone H2AX at Ser 139, termed γ-H2AX, was originally identified as an early event after the direct formation of DNA double-strand breaks (DSBs) by ionizing radiation. Now, the generation of γ-H2AX is also considered to occur in association with secondarily formed DSBs by cellular processing such as DNA replication and repair at the site of the initial damage, including DNA adducts, crosslinks, and UV-induced photolesions. Therefore, γ-H2AX is currently attracting attention as a new biomarker for detecting various genotoxic insults. We have determined the toxic impact of various environmental stresses such as chemicals, light and/or their coexposure using γ-H2AX, and found that the γ-H2AX assay exhibited high sensitivity and a low false-positive rate as a detection system of genotoxic potential. In this review, we introduced our recent findings concerning the evaluation of chemical phototoxicity, focusing on γ-H2AX.
Topics: Animals; DNA Damage; DNA Repair; Dermatitis, Phototoxic; Histones; Humans; Mutagenicity Tests; Phosphorylation
PubMed: 25480829
DOI: 10.1093/jrr/rru105 -
Archives of Pharmacal Research Apr 1999Melatonin (MLT), N-acetyl-5-methoxytryptamine, is mainly secreted by the pineal gland. The ultraviolet (UV), infrared (IR) and 1H-NMR spectra of irradiated and...
Melatonin (MLT), N-acetyl-5-methoxytryptamine, is mainly secreted by the pineal gland. The ultraviolet (UV), infrared (IR) and 1H-NMR spectra of irradiated and non-irradiated MLT were measured, and phototoxicity tests of MLT, anthracene (positive control) and sodium lauryl sulfate (SLS, negative control) were performed. The methods employed include both in vitro tests such as MTS assay using the human fibroblast cell and yeast growth inhibition assay using Candida albicans and in vivo method using the skin of guinea pig. UV absorption spectra and 1H-NMR spectra of MLT were changed by UVA (365 nm, 15 J/cm2), but IR spectra of MLT were not changed. The fifty percent inhibitor concentration (IC50) ratio (UV-/UV+) of MLT was 10. The inhibition zone of irradiated-paper disks treated with MLT was not observed. According to the results of histopathological examination, no pathologic lesion was observed in the non-irradiated group, but slight degeneration of keratinocytes in the epidermis, hemorrhage and vasodilation in dermis were observed in the irradiated group. These results indicate that the molecular structure of MLT is altered by UVA to unidentified photoproducts and a moderate phototoxicity of MLT is predicted.
Topics: Animals; Dermatitis, Phototoxic; Dose-Response Relationship, Drug; Guinea Pigs; Magnetic Resonance Spectroscopy; Male; Melatonin; Spectrophotometry, Ultraviolet
PubMed: 10230504
DOI: 10.1007/BF02976538 -
Alternatives To Laboratory Animals :... Oct 2007FRAME and the University of Nottingham have been in association for the past 25 years. During this time, the research in the FRAME Alternatives Laboratory (FAL) at the... (Review)
Review
FRAME and the University of Nottingham have been in association for the past 25 years. During this time, the research in the FRAME Alternatives Laboratory (FAL) at the University of Nottingham, which is partly funded by FRAME and also, more recently, by ECVAM, has involved participation in a number of international validation studies. Validation has become a pre-requisite for the regulatory acceptance of in vitro alternative test procedures, and a number of key lessons have been learned from these studies. The directors of validation studies need to ensure that standard operating procedures (SOPs) are fully complied with, and that the equipment used is certified to be of an acceptable standard. Database managers need to be able to check the original data, and to ensure adherence to procedures agreed before the study began. When the validation study is part of an integrated EU Framework Project, such as ACute-Tox, the Workpackage Leader must have the ability to understand and evaluate the data to be presented for inclusion in the study analysis, and to check that it complies with acceptance criteria. The potential to relate observed cellular biochemical changes to morphological endpoints also increases the level of understanding of the relevance and/or limitations of an assay. For example, exposure to a surfactant can induce the temporary loss of adhesion junctions between adjacent epithelial cells, resulting in the loss of barrier integrity and other effects on cell culture activity, which can potentially be restored over time. Unexpected results from the NRU phototoxicity assay with human keratinocytes instead of 3T3 cells, stimulated research into the ability of the in vitro assay, not only to identify phototoxins, but also to identify their possible mechanisms of action and mechanisms underlying the protective capacity within human primary keratinocytes in vitro. The protective effects of UV-filters can also be used to ascertain their effects on the photoactivation of drugs.
Topics: Animal Testing Alternatives; Animals; Dermatitis, Phototoxic; Humans; Toxicity Tests, Acute; Validation Studies as Topic
PubMed: 18001173
DOI: 10.1177/026119290703500502 -
Archivos de La Sociedad Espanola de... Sep 2021
Topics: Biological Assay; Dermatitis, Phototoxic; Humans; Retina
PubMed: 34479709
DOI: 10.1016/j.oftale.2021.01.006 -
Phototoxicity Secondary to Home Fireplace Exposure After Photodynamic Therapy for Actinic Keratosis.Cutis Oct 2021
Topics: Aminolevulinic Acid; Dermatitis, Phototoxic; Humans; Keratosis, Actinic; Photochemotherapy
PubMed: 34847013
DOI: 10.12788/cutis.0392 -
Journal of the American Academy of... Dec 2018Phototoxicity has been attributed to numerous oral drugs over the past 60 years.
BACKGROUND
Phototoxicity has been attributed to numerous oral drugs over the past 60 years.
OBJECTIVE
Determine the quality of evidence supporting suspected phototoxicity from oral drugs.
METHODS
The MEDLINE and EMBASE databases were searched for all studies that contain original data for drug-induced phototoxicity and were published between May 1959 and December 2016. Study quality was assessed by using a modified Grading of Recommendations, Assessment, Development and Evaluation scale.
RESULTS
The review included 240 eligible studies with a total of 2466 subjects. There were 1134 cases of suspected phototoxicity associated with 129 drugs. Most associations were supported by either very low-quality or low-quality evidence (89.1% of the studies). Medications supported by stronger evidence were vemurafenib, nonsteroidal anti-inflammatory drugs, and antibiotics, specifically, fluoroquinolones and tetracyclines. The most frequently reported drugs were vemurafenib, voriconazole, doxycycline, hydrochlorothiazide, amiodarone, and chlorpromazine. Photobiologic evaluation was performed in only 56 studies (23.3%), whereas challenge-rechallenge was done in 10% of cases.
LIMITATIONS
Only English-language publications were reviewed. Cases of phototoxicity that had been incorrectly categorized as photoallergy would not have been included.
CONCLUSIONS
Most purported associations between oral drugs and phototoxicity are not supported by high-quality evidence. Despite the variable quality of data, clinicians should be aware of the possible consequences of long-term use of culprit drugs.
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Dermatitis, Phototoxic; Evidence-Based Medicine; Humans; Vemurafenib
PubMed: 30003982
DOI: 10.1016/j.jaad.2018.06.061 -
Regulatory Toxicology and Pharmacology... Dec 2022The phototoxic potential of a number of furocoumarins is well established. On the other hand, studies have shown that bergamottin, a furocoumarin containing a bulky,...
The phototoxic potential of a number of furocoumarins is well established. On the other hand, studies have shown that bergamottin, a furocoumarin containing a bulky, hydrophobic side chain, has significantly less or is even absent of phototoxicity potential. The OECD Test Guideline 432 3T3/Neutral Red Uptake (NRU) in vitro phototoxicity test has shown to be a highly predictive test for identifying compounds that exhibit no phototoxicological potential. In this study using OECD 432, the established phototoxic furocoumarin 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP) and psoralen were phototoxic, whereas bergamottin showed no phototoxic potential. When compared to 5-MOP, 8-MOP and psoralen, bergamottin was clearly negative at molar-adjusted concentrations that were more than 9 times higher than those that produced phototoxicity in 8-MOP; nearly 16 times than those for psoralen and more than 36 times higher than those for 5-MOP. These data using in vitro 3T3 NRU Phototoxicity Test (OECD 432) are supportive of earlier studies showing bergamottin does not exhibit phototoxicological properties. The detection and quantification of bergamottin should therefore not contribute to the potential marker furocoumarins for risk management interventions intended to reduce the phototoxicity of natural furocoumarin containing preparations.
Topics: Humans; Methoxsalen; Organisation for Economic Co-Operation and Development; Ultraviolet Rays; Furocoumarins; Dermatitis, Phototoxic; Neutral Red
PubMed: 36288771
DOI: 10.1016/j.yrtph.2022.105281 -
International Journal of Dermatology Feb 2024
Topics: Humans; Tacrolimus; Vitiligo; Immunosuppressive Agents; Hypopigmentation; Dermatitis, Phototoxic; Treatment Outcome; Ointments
PubMed: 37670679
DOI: 10.1111/ijd.16837 -
La Revue Du Praticien Feb 2019
Topics: Dermatitis, Phototoxic; Diagnosis, Differential; Humans
PubMed: 30983220
DOI: No ID Found -
Nature Methods Jun 2017Are the answers to biological questions obtained via live fluorescence microscopy substantially affected by phototoxicity? Although a single set of standards for...
Are the answers to biological questions obtained via live fluorescence microscopy substantially affected by phototoxicity? Although a single set of standards for assessing phototoxicity cannot exist owing to the breadth of samples and experimental questions associated with biological imaging, we need quantitative, practical assessments and reporting standards to ensure that imaging has a minimal impact on observed biological processes and sample health. Here we discuss the problem of phototoxicity in biology and suggest guidelines to improve its reporting and assessment.
Topics: Animals; Cell Proliferation; Chlorocebus aethiops; DNA Damage; Dermatitis, Phototoxic; Free Radicals; Light; Microscopy, Fluorescence; Vero Cells
PubMed: 28661494
DOI: 10.1038/nmeth.4344