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In vitro tools for photobiological testing: molecular responses to simulated solar UV of keratinocytes growing as monolayers or as part of reconstructed skin

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Photochemical & Photobiological Sciences Vol - 9 Issue - 3

Photochemical & Photobiological Sciences Vol - 9 Issue - 2

Photochemical & Photobiological Sciences Vol -8

Photochemical & Photobiological Sciences Vol -7

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Photochemical & Photobiological Sciences Vol -5

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Photochemical & Photobiological Sciences Vol -2

In vitro tools for photobiological testing: molecular responses to simulated solar UV of keratinocytes growing as monolayers or as part of reconstructed skin

Content Provider	Royal Society of Chemistry (RSC)
Author	Marrot, Laurent Meunier, Jean-Roch Planel, Emilie Jones, Christophe Ginestet, Anne-Claire Belaïdi, Jean-Philippe
Copyright Year	2010
Abstract	Epidermal keratinocytes are critical targets for UV-induced genotoxicity as their transformation by sunlight overexposure can lead to skin cancer such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Therefore, assessment of photoprotection should involve early markers associated with DNA photodamage. Here, the same normal human keratinocytes either in monoculture (KC) or in full thickness reconstructed skin (RS) were compared with respect to their response to simulated solar UV (SSUV) exposure. Irradiation conditions (spectral power distribution and doses) were designed to mimic environmental zenithal UV from sunlight. At doses where survival was higher than 80%, comet assay showed more single strand breaks (SSB) and cyclobutane pyrimidine dimers (CPD) in keratinocytes in RS than in KC one hour post-exposure. The transcription factor p53 was activated in both models. While in KC p53 accumulation displayed a linear dose-dependency up to 24 h post-exposure, in RS it followed a bell-shaped profile and reverted to its basal rate. QRT-PCR demonstrated that among genes controlled by p53, P21 and MDM2 were clearly induced by SSUV in KC, whereas GADD45 expression was strongly and almost exclusively up-regulated in RS. Nrf2-dependent antioxidant genes (Ferritin light chain, NQO1) were only induced in RS, yet at low doses for NQO1. In vitro models such as KC or RS allowing the development of quantitative methodologies should be used as surrogates for in vivo tests assessing photogenotoxicity.
Starting Page	448
Ending Page	458
Page Count	11
File Format	HTM / HTML PDF
ISSN	1474905X
Volume Number	9
Issue Number	4
Journal	Photochemical & Photobiological Sciences
DOI	10.1039/b9pp00145j
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Spectral power distribution Carcinoma Genotoxicity Basal-cell carcinoma Antioxidant Comet assay Skin cancer Monoculture Pyrimidine dimer P53 SCC DNA Gadd45 Irradiation Mdm2 Cyclobutane Ferritin light chain Transcription factor Photoprotection Real-time polymerase chain reaction NFE2L2
Content Type	Text
Resource Type	Article
Subject	Physical and Theoretical Chemistry

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Cyclobutane pyrimidine dimers form preferentially at the major p53 mutational hotspot in UVB-induced mouse skin tumors

Relationship between UV-induced mutant p53 patches and skin tumours, analysed by mutation spectra and by induction kinetics in various DNA-repair-deficient mice

Comparative Medicine (2009)

UVA-induced cyclobutane pyrimidine dimers in DNA: a direct photochemical mechanism?

p53 mutant human glioma cells are sensitive to UV-C-induced apoptosis due to impaired cyclobutane pyrimidine dimer removal.

Binds to and cleaves sp (5-thyminyl-5,6-dihydrothymine) but not cyclobutane pyrimidine dimers in uv-irradiated dna (2000).

Octyl methoxycinnamate modulates gene expression and prevents cyclobutane pyrimidine dimer formation but not oxidative dna (2009).

The CaSR Modulator NPS-2143 Reduced UV-Induced DNA Damage in Skh:hr1 Hairless Mice but Minimally Inhibited Skin Tumours.

In vivo recruitment of xpc to uv-induced cyclobutane pyrimidine.

In vitro tools for photobiological testing: molecular responses to simulated solar UV of keratinocytes growing as monolayers or as part of reconstructed skin

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In vitro tools for photobiological testing: molecular responses to simulated solar UV of keratinocytes growing as monolayers or as part of reconstructed skin