Development and characterization of an in vivo skin photomicronucleus assay in rats
| Autor: | Astrid A. Reus, Sharon Robinson, Ingrid Pruimboom-Brees, Anthony M. Lynch, Richard N. C. van Meeuwen, Mustafa Usta, Wilfred J. M. Maas, Cyrille Krul, Peter Clements, Julia Kenny |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Micronucleus Tests Health Toxicology and Mutagenesis Early detection Dose-Response Relationship Radiation Epithelial Cells Context (language use) Mutagen Pharmacology Biology Toxicology medicine.disease_cause In vitro Rats Rats Sprague-Dawley In vivo Genetics medicine Animals Methoxsalen Micronucleus Genetics (clinical) Genotoxicity Target organ Skin |
| Zdroj: | Mutagenesis. 25:407-416 |
| ISSN: | 1464-3804 0267-8357 |
| DOI: | 10.1093/mutage/geq023 |
| Popis: | For pharmaceuticals, current regulatory guidance for photosafety testing states that studies are warranted for drug candidates that both absorb light in the range of 290-700 nm and that are either applied topically or reach the skin or eyes by systemic exposure. In contrast to standard genotoxicity evaluations, where a positive (or equivocal) result in vitro can be placed into context with additional testing in vivo, there are no equivalent short-term in vivo photogenotoxicity assays in the current photosafety test battery. Therefore, a short-term in vivo assay for the evaluation of a photogenotoxic potential in the skin, the target organ for photocarcinogenicity, was developed in rats. After oral 8-methoxypsoralen administration, rats were exposed to ultraviolet radiation and sacrificed 3 days after treatment to isolate epidermal cells for subsequent micronucleus (MN) evaluation. Optimal conditions were determined to obtain maximal induction of MN, followed by demonstrating feasibility and reproducibility of the method. The results of the present study indicate that the in vivo rat skin photomicronucleus test may be a promising tool for detection of photoclastogenicity. Given the association between MN induction and cancer, the assay may also provide a promising tool for the early detection of photocarcinogenesis and help bridge the gap in the existing photosafety testing paradigm. © The Author 2010. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. |
| Databáze: | OpenAIRE |
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