Print Email Facebook Twitter The in vivo rat skin photomicronucleus assay: Phototoxicity and photogenotoxicity evaluation of six fluoroquinolones Title The in vivo rat skin photomicronucleus assay: Phototoxicity and photogenotoxicity evaluation of six fluoroquinolones Author Reus, A.A. Usta, M. Kenny, J.D. Clements, P.J. Pruimboom-Brees, I. Aylott, M. Lynch, A.M. Krul, C.A.M. Publication year 2012 Abstract An in vivo photomicronucleus test (MNT) using rat skin, the target organ for photoirritancy and carcinogenicity, was recently described. The assay was evaluated using fluoroquinolone (FQ) antibiotics with varying degrees of phototoxic potency (i.e. sparflocacin [SPFX], lomefloxacin [LOFX], ciprofloxacin [CIFX], levofloxacin [LEFX], gemifloxacin [GEFX] and gatifloxacin [GAFX]) using a solar simulator producing both UVA and UVB (ratio 23:1). Experiments were performed at The Netherlands Organisation for Applied Scientific Research (TNO) and GlaxoSmithKline (GSK) to investigate interlaboratory variability, including evaluation of phototoxicity (clinical signs), micronucleus induction and histopathology. The potency of micronuclei (MN) formation in rat skin induced by the FQs was SPFX = LOFX > CIFX = LEFX, however, MN induction was only statistically significant for SPFX and LOFX. In both laboratories, GEFX and GAFX did not increase the MN frequencies compared to the irradiated vehicle control. Signs of phototoxicity, including clinical and histopathological changes, were observed with SPFX and LOFX to a similar degree as the positive control, 8-methoxypsoralen. In addition, there were some clinical signs of phototoxicity seen with CIFX, LEFX, GEFX and GAFX, but not always in both laboratories for CIFX, GEFX and GAFX and when observed, these were considered only mild. Of these, only LEFX also showed histopathological changes. In all studies, photogenotoxic potency correlated with photocarcinogenic potential and moreover, photogenotoxicity was not observed in the absence of phototoxicity. The results of the TNO/GSK study indicate that the in vivo rat skin photoMNT may be a promising tool for detection of photoclastogencity and photoirritancy in the skin/eye in the same animal. Given the association between the MNT and cancer, the skin photoMNT 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 2012. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. Subject Triskelion BVTARA - Toxicology and Risk AssessmentTNO BedrijvenBiomedical InnovationResearchHealthy Livingciprofloxacingatifloxacingemifloxacinlevofloxacinlomefloxacinmethoxsalenquinoline derived antiinfective agentsparfloxacinanimal tissuearticlecarcinogenicitycontrolled studyepidermis cellfemalegenotoxicityhairless mousehistopathologyin vitro studyin vivo studymicronucleusmicronucleus testnonhumanphototoxicitypriority journalratsingle drug doseskinSprague Dawley rat To reference this document use: http://resolver.tudelft.nl/uuid:89d58ebb-a2a7-4a1c-a0d6-8e7363828b00 DOI https://doi.org/10.1093/mutage/ges038 TNO identifier 466454 ISSN 0267-8357 Source Mutagenesis, 27 (6), 721-729 Bibliographical note Chemicals/CAS: ciprofloxacin, 85721-33-1; gatifloxacin, 112811-59-3, 180200-66-2; gemifloxacin, 175463-14-6, 204519-65-3, 210353-53-0, 210353-55-2, 210353-56-3; levofloxacin, 100986-85-4, 138199-71-0; lomefloxacin, 98079-51-7; methoxsalen, 298-81-7, 8004-26-0; sparfloxacin, 111542-93-9 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.