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Proteomic analysis of haptenation by skin sensitisers: Diphencyprone and ethyl acrylate

Proteomic analysis of haptenation by skin sensitisers: Diphencyprone and ethyl acrylate
Proteomic analysis of haptenation by skin sensitisers: Diphencyprone and ethyl acrylate
The potential risk of skin sensitisation, associated with the development of allergic contact dermatitis (ACD), is a consideration in the safety assessment of new ingredients for use in personal care products. Protein haptenation in skin by sensitising chemicals is the molecular initiating event causative of skin sensitisation. Current methods for monitoring skin sensitisation rely on limited reactivity assays, motivating interest in the development of proteomic approaches to characterise the skin haptenome. Increasing our mechanistic understanding of skin sensitisation and ACD using proteomics presents an opportunity to develop non-animal predictive methods and/or risk assessment approaches. Previously, we have used a novel stable isotope labelling approach combined with data independent mass spectrometry (HDMSE) to characterise the haptenome for a number of well-known sensitisers. We have now extended this work by characterising the haptenome of the sensitisers Diphenylcyclopropenone (DPCP) and Ethyl Acrylate (EA) with the model protein Human Serum Albumin (HSA) and the complex lysates of the skin keratinocyte, HaCaT cell line. We show that haptenation in complex nucleophilic models is not random, but a specific, low level and reproducible event. Proteomic analysis extends our understanding of sensitiser reactivity beyond simple reactivity assays and offers a route to monitoring haptenation in living cells.
Acrylates/toxicity, Cell Line, Cyclopropanes/toxicity, Dermatitis, Allergic Contact/immunology, Haptens/chemistry, Humans, Immunization, Mass Spectrometry, Models, Molecular, Proteins/chemistry, Proteomics/methods, Serum Albumin/chemistry, Skin/drug effects
0887-2333
104697
Parkinson, Erika
b7294dcc-43d3-46c4-bd19-7f6795b80fe6
Aleksic, Maja
152a8f09-84c2-4ebb-94c7-79c31edf53aa
Arthur, Rachael
b595bf5a-7c08-426e-9992-8b12c5e95817
Regufe Da Mota, Sergio
fe39404b-e413-4834-97c6-0f2204b500a9
Cubberley, Richard
e436b046-0d24-4503-bc78-8122f3bf14a8
Skipp, Paul J.
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Parkinson, Erika
b7294dcc-43d3-46c4-bd19-7f6795b80fe6
Aleksic, Maja
152a8f09-84c2-4ebb-94c7-79c31edf53aa
Arthur, Rachael
b595bf5a-7c08-426e-9992-8b12c5e95817
Regufe Da Mota, Sergio
fe39404b-e413-4834-97c6-0f2204b500a9
Cubberley, Richard
e436b046-0d24-4503-bc78-8122f3bf14a8
Skipp, Paul J.
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5

Parkinson, Erika, Aleksic, Maja, Arthur, Rachael, Regufe Da Mota, Sergio, Cubberley, Richard and Skipp, Paul J. (2020) Proteomic analysis of haptenation by skin sensitisers: Diphencyprone and ethyl acrylate. Toxicology in Vitro, 62, 104697, [104697]. (doi:10.1016/j.tiv.2019.104697).

Record type: Article

Abstract

The potential risk of skin sensitisation, associated with the development of allergic contact dermatitis (ACD), is a consideration in the safety assessment of new ingredients for use in personal care products. Protein haptenation in skin by sensitising chemicals is the molecular initiating event causative of skin sensitisation. Current methods for monitoring skin sensitisation rely on limited reactivity assays, motivating interest in the development of proteomic approaches to characterise the skin haptenome. Increasing our mechanistic understanding of skin sensitisation and ACD using proteomics presents an opportunity to develop non-animal predictive methods and/or risk assessment approaches. Previously, we have used a novel stable isotope labelling approach combined with data independent mass spectrometry (HDMSE) to characterise the haptenome for a number of well-known sensitisers. We have now extended this work by characterising the haptenome of the sensitisers Diphenylcyclopropenone (DPCP) and Ethyl Acrylate (EA) with the model protein Human Serum Albumin (HSA) and the complex lysates of the skin keratinocyte, HaCaT cell line. We show that haptenation in complex nucleophilic models is not random, but a specific, low level and reproducible event. Proteomic analysis extends our understanding of sensitiser reactivity beyond simple reactivity assays and offers a route to monitoring haptenation in living cells.

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DPCP_and_EA_draft_manuscript_Revision_clean (1) - Accepted Manuscript
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More information

Accepted/In Press date: 21 October 2019
e-pub ahead of print date: 24 October 2019
Published date: February 2020
Keywords: Acrylates/toxicity, Cell Line, Cyclopropanes/toxicity, Dermatitis, Allergic Contact/immunology, Haptens/chemistry, Humans, Immunization, Mass Spectrometry, Models, Molecular, Proteins/chemistry, Proteomics/methods, Serum Albumin/chemistry, Skin/drug effects

Identifiers

Local EPrints ID: 436056
URI: http://eprints.soton.ac.uk/id/eprint/436056
ISSN: 0887-2333
PURE UUID: 38e5b6e0-ce7c-419d-87f0-25c255a2e986
ORCID for Sergio Regufe Da Mota: ORCID iD orcid.org/0000-0002-8127-5246
ORCID for Paul J. Skipp: ORCID iD orcid.org/0000-0002-2995-2959

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Date deposited: 27 Nov 2019 17:30
Last modified: 17 Mar 2024 05:05

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Contributors

Author: Erika Parkinson
Author: Maja Aleksic
Author: Rachael Arthur
Author: Sergio Regufe Da Mota ORCID iD
Author: Richard Cubberley
Author: Paul J. Skipp ORCID iD

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