Mol M A, van der Schans G P, Lohman P H
TNO Medical Biological Laboratory, Rijswijk, The Netherlands.
Mutat Res. 1993 Oct;294(3):235-45. doi: 10.1016/0921-8777(93)90006-3.
The induction of DNA interstrand cross-links and their repair has been studied in cultured human epidermal keratinocytes exposed to sulfur mustard, bis-(beta-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 microM sulfur mustard approximately 0.05 SSB (and/or ALS)/10(9) Da of DNA and approximately 0.12 cross-links/10(9) 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 microM, repair seems to occur not at all.
已经在暴露于硫芥（双（β-氯乙基）硫醚）的培养人表皮角质形成细胞中研究了DNA链间交联的诱导及其修复。碱性洗脱是定量测定DNA链间交联数量最敏感的方法。然而，对于硫芥而言，这些数据的可靠性会较低，因为硫芥还会诱导DNA单链断裂（SSB）和/或碱不稳定位点（ALS）。硫芥诱导的SSB和/或ALS的频率通过免疫化学方法测定。校正硫芥诱导的SSB和/或ALS后，计算出的交联数量大幅增加。我们的结果表明，每微摩尔硫芥在暴露后立即诱导约0.05个SSB（和/或ALS）/10⁹ Da的DNA和约0.12个交联/10⁹ Da的DNA。大多数DNA链间交联在暴露后的前24小时内被去除，但少数损伤似乎持续存在。在暴露于低至1微摩尔硫芥浓度的细胞中，似乎根本不发生修复。
