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A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests

Johansson, Henrik LU ; Lindstedt, Malin LU ; Albrekt, Ann-Sofie LU and Borrebaeck, Carl LU (2011) In BMC Genomics 12.
Abstract
Background: Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power. Results: We have developed a novel cell-based assay for the prediction of... (More)
Background: Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power. Results: We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization. Conclusions: A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional animal-based tests. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
BMC Genomics
volume
12
publisher
BioMed Central
external identifiers
  • wos:000295274800001
  • scopus:79961120567
ISSN
1471-2164
DOI
10.1186/1471-2164-12-399
language
English
LU publication?
yes
id
6e4b696c-2c59-406b-b96e-e365b9d2dc34 (old id 2179661)
date added to LUP
2011-10-28 10:50:08
date last changed
2017-09-17 05:46:13
@article{6e4b696c-2c59-406b-b96e-e365b9d2dc34,
  abstract     = {Background: Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power. Results: We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization. Conclusions: A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional animal-based tests.},
  author       = {Johansson, Henrik and Lindstedt, Malin and Albrekt, Ann-Sofie and Borrebaeck, Carl},
  issn         = {1471-2164},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {BMC Genomics},
  title        = {A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests},
  url          = {http://dx.doi.org/10.1186/1471-2164-12-399},
  volume       = {12},
  year         = {2011},
}