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Studies on the methyl isocyanate adducts with globin
1Centre of Industrial Hygiene and Occupational Diseases, National Institute of Public Health, Srobárova 48, 10042 Prague 10, Czech Republic. jmraz@szu.cz
Chemico-Biological Interactions
|June 30, 2004
Summary
This study identified methylisocyanate (MIC) adducts in human globin, revealing N-terminal Val and Lys side-chains as primary binding sites. These findings support biomonitoring of isocyanate exposure through protein adduct analysis.
Area of Science:
- Toxicology
- Biochemistry
- Analytical Chemistry
Background:
- Isocyanates, like methylisocyanate (MIC), are reactive compounds forming adducts with biological macromolecules.
- Biomonitoring of isocyanate exposure via protein adducts is challenging but valuable for assessing internal exposure.
Purpose of the Study:
- To characterize methylisocyanate (MIC) adducts formed in human globin.
- To explore the potential of these adducts as biomarkers for isocyanate exposure, including industrial solvents like DMF and MF.
Main Methods:
- Human globin was treated with MIC and enzymatically hydrolyzed.
- High-performance liquid chromatography with atmospheric pressure chemical ionization mass spectrometry (HPLC/APCI-MS) was used for adduct analysis.
- Adducts were identified by comparing with synthetic standards and analyzing MS/MS spectra.
Main Results:
- Major MIC adducts were identified at the N-terminal Val and Lys side-chain of human globin.
- Approximately 20 other adducts were observed, with some tentatively identified.
- MIC adducts were also detected in rat globin after exposure to N,N-dimethylformamide (DMF) and N-methylformamide (MF).
Conclusions:
- The study successfully characterized MIC-globin adducts, with Val and Lys adducts being key.
- The presence of MIC adducts in DMF/MF-exposed rats suggests their utility as biomarkers for occupational exposure.
- Further studies are warranted to validate the Lys adduct as a biomarker for human DMF exposure.