Title
Mass spectrometric identification of isocyanate-induced modifications of keratins in human skin
Author
Hulst, A.G.
Verstappen, D.R.W.
van der Riet-van Oeveren, D.
Vermeulen, N.P.E.
Noort, D.
Publication year
2015
Abstract
In the current paper we show that exposure of human callus to isocyanates leads to covalent modifications within keratin proteins. Mass spectrometric analyses of pronase digests of keratin isolated from exposed callus show that both mono- and di-adducts (for di-isocyanates) are predominantly formed on the ε-amino group of lysine. In addition, numerous modified tryptic keratin fragments were identified, demonstrating rather random lysine modification. Interestingly, preliminary experiments demonstrate that in case of MDI a similar lysine di-adduct was formed with lung elastin. Our data support the hypothesis that skin sensitization through antigenic modifications of skin proteins by isocyanates could play a role in occupational isocyanate-induced asthma. It is further envisaged that the elucidated adducts will also have great potential for use as biomarkers to assess skin exposure to isocyanates. Advantageously, the various lysine adducts display the presence of a characteristic daughter fragment at m/z 173.1 [lysine-NCO]+, enabling generic and rapid screening for exposure to isocyanates. © 2015 Elsevier Ireland Ltd. All rights reserved.
Subject
Observation, Weapon & Protection Systems
CBRN - CBRN Protection
TS - Technical Sciences
Adducts
Biomarkers
Exposure assessment
Isocyanates
Keratin
Skin
2 methacryloyloxethyl isocyanate
2 nitrophenylisocyanate
2,6 toluene diisocyanate
4 bromophenylisocyanate
Allylisocyanate
Biological marker
Elastin
Isocyanic acid derivative
Keratin
Lysine
Methylene diphenyl diisocyanate
Phenethylisocyanate
Pronase
Unclassified drug
Antigenicity
Asthma
Callus
Exposure
Human
Human tissue
Mass spectrometry
Protein analysis
Protein isolation
Protein modification
Skin sensitization
To reference this document use:
http://resolver.tudelft.nl/uuid:83ca34ac-b77a-496b-bf3d-74535de9a039
DOI
https://doi.org/10.1016/j.cbi.2015.06.008
TNO identifier
527063
Publisher
Elsevier Ireland Ltd
ISSN
0009-2797
Source
Chemico-Biological Interactions, 237, 141-150
Document type
article