Genes specifically modulated in sensitized skins allow the detection of sensitizers in a reconstructed human skin model. Development of the SENS-IS assay

被引：71

作者：

Cottrez, Francoise ^{[1
]}

Boitel, Elodie ^{[1
]}

Auriault, Claude ^{[1
]}

Aeby, Pierre ^{[1
]}

Groux, Herve ^{[1
]}

机构：

[1] ImmunoSearch, Les Cyclades, Grasse, France

来源：

TOXICOLOGY IN VITRO | 2015年 / 29卷 / 04期

关键词：

Skin sensitization; Alternatives to animal tests; Toxicogenomics; Reconstituted epidermis; SENS-IS; DENDRITIC CELL MATURATION; TRANSCRIPTION FACTOR NRF2; CONTACT HYPERSENSITIVITY; COSTIMULATORY MOLECULES; CHEMICAL SENSITIZERS; PEPTIDE REACTIVITY; EXPRESSION; LINE; DERMATITIS; ACTIVATION;

D O I：

10.1016/j.tiv.2015.02.012

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

Analysis of genes modulated during the sensitization process either on mice (LLNA) or human (blisters) combined with data mining has allowed the definition of a comprehensive panel of sensitization biomarkers. This set of genes includes already identified markers such as the ARE family and others not yet associated with the sensitization process (the so-called SENS-IS gene subset). The expression of this set of genes has been measured on reconstituted human epidermis models (Episkin) exposed to various sensitizers and non-sensitizers. Fine analysis of their expression pattern indicates that it is the number of modulated genes rather than the intensity of up-regulation that correlates best with the sensitization potential of a chemical. Moreover, sensitizers that are weak inductors of ARE genes tend to be relevant modulators of the SENS-IS subset. By combining the expression data obtained with both gene subsets, it is now possible to identify a wide variety of sensitizers on a test system (in vitro reconstructed human epidermis) that is very similar to the in vivo situation and compatible with a large variety of test substance characteristics. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：787 / 802

页数：16

共 3 条

[1] Further development and validation of the in vitro micronucleus assay in the EpiDerm™ 3D reconstructed human skin model.
Hu, T.
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Curren, R. D.
Aardema, M. J.
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, 2007, 48 (07) : 596 - 596
[2] The development of an inhouse reconstructed human epidermis (RhE) and performance as a skin irritation model.
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Schwarzer, A. C.
Silva, M. A.
Trindade, E. S.
Leme, D. M.
Pestana, C.
TOXICOLOGY LETTERS, 2019, 314 : S306 - S306
[3] Development of a GLP 3-D EpiDerm™ Reconstructed Human Skin Micronucleus Assay: A Promising Animals-Alternative Model
Roy, S.
Szkudlinska, A.
Wang, K.
Shi, J.
Hickman, S.
Madraymootoo, W.
Aardema, M. J.
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, 2012, 53 : S42 - S42

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