Quantification of sulfur mustard-induced DNA interstrand cross-links and single-strand breaks in cultured human epidermal keratinocytes

article


Mol, M.A.E.

Schans, G.P. van der

Lohman, P.H.M.
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.
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Alkaline elutionDNA single-strand breaksKeratinocytesSulfur mustardSingle stranded dnaDNA cross linkingDNA repairDNA strand breakageHumanHuman cellCells, CulturedCross-Linking ReagentsDNADNA damageCross-Linking ReagentsDNA, 9007-49-2Mustard Gas, 505-60-2
TNO Identifier
36693
Repository link
https://resolver.tno.nl/uuid:017ac3a6-ecec-4525-b0f3-bd38c36faff8
ISSN
0921-8777
Source
Mutation Research, 294, pp. 235-245.
Pages
235-245
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