PMID- 35570235
OWN - NLM
STAT- MEDLINE
DCOM- 20220624
LR  - 20220716
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Print)
IS  - 0340-5761 (Linking)
VI  - 96
IP  - 8
DP  - 2022 Aug
TI  - Highly stable peptide adducts from hard keratins as biomarkers to verify local 
      sulfur mustard exposure of hair by high-resolution mass spectrometry.
PG  - 2287-2298
LID - 10.1007/s00204-022-03307-0 [doi]
AB  - In the recent past, the blister agent sulfur mustard (SM) deployed by the 
      terroristic group Islamic State has caused a huge number of civilian and military 
      casualties in armed conflicts in the Middle East. The vaporized or aerolized 
      agent might be inhaled and have direct contact to skin and hair. Reaction 
      products of SM with plasma proteins (adducts) represent well-established systemic 
      targets for the bioanalytical verification of exposure. The SM-derived 
      hydroxyethylthioethyl (HETE)-moiety is attached to nucleophilic amino acid side 
      chains and allows unambiguous adduct detection. For shipping of common blood and 
      plasma samples, extensive packaging rules are to be followed as these matrices 
      are considered as potentially infectious material. In contrast, hair is 
      considered as non-infectious thus making its handling and transportation much 
      less complicated. Therefore, we addressed this matrix to develop a procedure for 
      bioanalytical verification. Following optimized lysis of SM-treated human scalp 
      hair and pepsin-catalyzed proteolysis of adducts of keratin type I and II, 
      microbore liquid chromatography-electrospray ionization 
      high-resolution tandem-mass spectrometry (microLC-ESI MS/HR MS) was used to detect 
      three alkylated keratin-derived biomarker peptides: AE(-HETE)IRSDL, 
      FKTIE(-HETE)EL, and LE(-HETE)TKLQF simultaneously. All bear the HETE-moiety bound 
      to a glutamic acid residue. Protein adducts were stable for at least 14 weeks at 
      ambient temperature and contact to air, and were not affected by washing the hair 
      with shampoo. The biomarker peptides were also obtained from beard, armpit, 
      abdominal, and pubic hair. This is the first report introducing stable local 
      peptide adduct biomarkers from hair, that is easily accessible by a non-invasive 
      sampling process.
CI  - (c) 2022. The Author(s).
FAU - Schmeisser, Wolfgang
AU  - Schmeisser W
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, 
      Munich, Germany.
FAU - Siegert, Markus
AU  - Siegert M
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, 
      Munich, Germany.
AD  - Department of Chemistry, Humboldt-Universitat Zu Berlin, Brook-Taylor-Strasse 2, 
      12489, Berlin, Germany.
AD  - Proteros Biostructures GmbH, Bunsenstrasse 7a, 82152, Planegg, Germany.
FAU - Thiermann, Horst
AU  - Thiermann H
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, 
      Munich, Germany.
FAU - Rein, Theo
AU  - Rein T
AD  - Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804, Munich, 
      Germany.
FAU - John, Harald
AU  - John H
AUID- ORCID: 0000-0002-7126-6709
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, 
      Munich, Germany. HaraldJohn@bundeswehr.org.
LA  - eng
GR  - GRK 2338/Deutsche Forschungsgemeinschaft/
PT  - Journal Article
DEP - 20220516
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Biomarkers)
RN  - 0 (Chemical Warfare Agents)
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 0 (Peptides)
RN  - 68238-35-7 (Keratins)
RN  - T8KEC9FH9P (Mustard Gas)
RN  - ZIF514RVZR (Serum Albumin, Human)
SB  - IM
MH  - Biomarkers
MH  - *Chemical Warfare Agents/chemistry
MH  - Hair/chemistry
MH  - Humans
MH  - Hydroxyeicosatetraenoic Acids
MH  - Keratins
MH  - *Mustard Gas/chemistry/toxicity
MH  - Peptides
MH  - Serum Albumin, Human/chemistry
MH  - Spectrometry, Mass, Electrospray Ionization
MH  - Tandem Mass Spectrometry/methods
PMC - PMC9217830
OTO - NOTNLM
OT  - Hydroxyethylthioethyl-moiety
OT  - Organisation for the Prohibition of Chemical Weapons
OT  - Peptide biomarker
OT  - Protein adducts
OT  - Vesicant
COIS- The authors declare no conflict of interest.
EDAT- 2022/05/16 06:00
MHDA- 2022/06/25 06:00
PMCR- 2022/05/16
CRDT- 2022/05/15 23:15
PHST- 2022/01/26 00:00 [received]
PHST- 2022/04/27 00:00 [accepted]
PHST- 2022/05/16 06:00 [pubmed]
PHST- 2022/06/25 06:00 [medline]
PHST- 2022/05/15 23:15 [entrez]
PHST- 2022/05/16 00:00 [pmc-release]
AID - 10.1007/s00204-022-03307-0 [pii]
AID - 3307 [pii]
AID - 10.1007/s00204-022-03307-0 [doi]
PST - ppublish
SO  - Arch Toxicol. 2022 Aug;96(8):2287-2298. doi: 10.1007/s00204-022-03307-0. Epub 
      2022 May 16.