Title
Quantification of sulfur mustard-induced DNA interstrand cross-links and single-strand breaks in cultured human epidermal keratinocytes
Author
Mol, M.A.E.
van der Schans, G.P.
Lohman, P.H.M.
Centraal Instituut voor Voedingsonderzoek TNO Medisch Biologisch Laboratorium TNO
Publication year
1993
Abstract
The induction of DNA interstrand cross-links and their repair has been studied in cultured human epidermal keratinocytes exposed to sulfur mustard, bis-(β-chloroethyl)sulfide. Alkaline elution is the most sensitive method to determine the number of DNA interstrand cross-links quantitatively. However, in the case of sulfur mustard the reliability of these data will be less since sulfur mustard also induces DNA single-strand breaks (SSB) and/or alkali-labile sites (ALS). The frequency of SSB and/or ALS induced by sulfur mustard is determined immunochemically. Correction for the induction of SSB and/or ALS induced by sulfur mustard resulted in a substantial increase in the calculated number of cross-links. Our results indicate that per μM sulfur mustard approximately 0.05 SSB (and/or ALS)/109 Da of DNA and approximately 0.12 cross-links/109 Da of DNA were induced immediately after exposure. Most of the DNA interstrand cross-links are removed during the first 24 h post exposure, but a small number of lesions seem to be persistent. In cells exposed to sulfur mustard concentrations as low as 1 μM, repair seems to occur not at all.
Subject
Alkaline elution
DNA single-strand breaks
Keratinocytes
Sulfur mustard
Single stranded dna
DNA cross linking
DNA repair
DNA strand breakage
Human
Human cell
Cells, Cultured
Cross-Linking Reagents
DNA
DNA damage
Cross-Linking Reagents
DNA, 9007-49-2
Mustard Gas, 505-60-2
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DOI
https://doi.org/10.1016/0921-8777(93)90006-3
TNO identifier
36693
ISSN
0921-8777
Source
Mutation Research, 294, 235-245
Document type
article