The Second ECVAM Workshop on Phototoxicity Testing

Spielmann, Horst; Müller, Lutz; Averbeck, D.; Balls, Michael; Brendler‐Schwaab, Susanne; Castell, José V.; Curren, Rodger; Silva, Odile De; Gibbs, Neil K.; Liebsch, Manfred; Lovell, W.W.; Merk, Hans F.; Nash, John J.; Neumann, Norbert; Pape, Wolfgang; Ulrich, Peter; Vohr, Hans-Werner

doi:10.1177/026119290002800603

Cited by 48 publications

(4 citation statements)

References 95 publications

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“…Since March 2009 chemically-induced phototoxicity has had to be studied only in vitro. For this purpose, a validated test based on neutral red uptake by 3T3 fibroblasts in culture after exposure to solar UV or UVA in the presence of the chemical to be studied (3T3 NRU test 29 ) has been developed. In order to better characterize phototoxicity, many efforts have been made to develop screening strategies involving reconstructed epidermis in addition to 3T3 NRU assay.…”

Section: Introductionmentioning

confidence: 99%

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

Marrot

Planel

Ginestet

et al. 2010

Photochem Photobiol Sci

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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.

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Section: Introductionmentioning

confidence: 99%

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

Marrot

Planel

Ginestet

et al. 2010

Photochem Photobiol Sci

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“…For this purpose, different symposia, meetings and workshops have been organized since 1993, by the European Center for the Validation of Alternative Methods in 1993 (3) and 1999 (4) in Europe, in 1996 by the Food and Drug Administration (5) and in 1999 (International Workshop of Genotoxicity Test Procedures, IWGTP, Washington) (6), to address this question and evaluate the existing in vitro methodology. No regulatory requirement has been specified, but a set of recommendations and guidances have been issued (4–6). Until now, the photocytotoxicity test 3T3 neutral red uptake (NRU) is the only in vitro method that has been validated so far by European regulatory affairs (7–9).…”

Section: Introductionmentioning

confidence: 99%

Photogenotoxicity of Mammalian Cells: A Review of the Different Assays for In Vitro Testing¶

Meunier

Sarasin

Marrot

2007

Photochemistry and Photobiology

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During the past several years, phototoxicity has been studied at the molecular level, and these studies have provided new insights in the field of DNA lesion characterization, DNA repair and cell response to ultraviolet (UV)‐induced stress. The development of new antibiotics and antiinflammatory drugs has highlighted the necessity to develop the assessment of phototoxicity in the safety evaluation of new chemical compounds. This paper aims at reviewing the known molecular mechanisms of the cellular response to UV‐induced stress, the in vitro methods that can be proposed and used to screen for toxicity of sunlight and the photosensitization process resulting from the activation of drugs by light. UV sources, biological systems and endpoints of interest in that particular objective are listed. Phototoxic effects span from the cytotoxic–apoptotic effect to the induction of primary DNA damage, DNA repair and a variety of stress genes acting on the cell cycle and the fate of the cell. Ultimately, it can lead to the induction of hereditary DNA modification. A variety of assays are proposed to specifically address all these particular consequences of UV‐induced toxicity.

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“…There are hundreds of cannabinoid receptors agonists with varying affinities for CB1 that can be used as potential targets for addictive drugs [31]. In this study, we investigated whether the synthetic cannabinoid JWH-210, which has a high affinity for CB1, increases the dependence liability of other abused drugs, such as methamphetamine (METH) [32]. In addition, we also investigated how CB1 agonist affects neurotransmitters, such as dopamine, which are involved in impulsive behaviors and psychological dependence that may result from substance abuse.…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid Receptor Type 1 Regulates Drug Reward Behavior via Glutamate Decarboxylase 67 Transcription

Seo

Park

et al. 2021

IJMS

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Interaction of cannabinoid receptor type 1 (CB1) and GABAergic neuronal activity is involved in drug abuse-related behavior. However, its role in drug-dependent Pavlovian conditioning is not well understood. In this study, we aimed to evaluate the effects of a CB1 agonist, JWH-210, on the development of conditioned place preference (CPP)-induced by methamphetamine (METH). Pretreatment with a synthetic cannabinoid, JWH-210 (CB1 agonist), increased METH-induced CPP score and METH-induced dopamine release in acute striatal slices. Interestingly, CB1 was expressed in glutamate decarboxylase 67 (GAD67) positive cells, and overexpression of CB1 increased GAD67 expression, while CB1 knockdown reduced GAD67 expression in vivo and in vitro. GAD67 is known as an enzyme involved in the synthesis of GABA. CB1 knockdown in the mice striatum increased METH-induced CPP. When GAD67 decreased in the mice striatum, mRNA level of CB1 did not change, suggesting that CB1 can regulate GAD67 expression. GAD67 knockdown in the mouse striatum augmented apomorphine (dopamine receptor D2 agonist)–induced climbing behavior and METH-induced CPP score. Moreover, in the human brain, mRNA level of GAD67 was found to be decreased in drug users. Therefore, we suggest that CB1 potentiates METH-induced CPP through inhibitory GABAergic regulation of dopaminergic neuronal activity.

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The Second ECVAM Workshop on Phototoxicity Testing

Cited by 48 publications

References 95 publications

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

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

Photogenotoxicity of Mammalian Cells: A Review of the Different Assays for In Vitro Testing¶

Cannabinoid Receptor Type 1 Regulates Drug Reward Behavior via Glutamate Decarboxylase 67 Transcription

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