Lin P, Vaughan F L, Bernstein I A
Department of Environmental and Industrial Health, University of Michigan, Ann Arbor 48109, USA.
Biochem Biophys Res Commun. 1996 Jan 17;218(2):556-61. doi: 10.1006/bbrc.1996.0099.
Interstrand cross-links in the DNA of epidermal basal keratinocytes may be responsible for cell death and consequent vesication in skin exposed to BCES. The formation of cross-links and cytotoxicity were compared when cells in primary monolayer cultures of rat epidermal keratinocytes, synchronized at the G1/S boundary or in the G1 phase of the cell cycle, were exposed to BCES. The dose-responsive formation of cross-links, measured with an ethidium bromide-fluorescence assay, was determined immediately after exposure of cells at either position of the cycle. At 24 hr post-exposure, the level of cross-links in cells exposed at the G1 phase showed had not decreased significantly and was still dose-dependent. However, cells exposed in the G1 phase showed a major decrease in cross-links. Formation of interstrand DNA cross-links appears to be related to the mustard's cytotoxicity.
表皮基底角质形成细胞DNA中的链间交联可能是接触双(2-氯乙基)硫醚的皮肤中细胞死亡及随后出现水疱的原因。当处于细胞周期G1/S边界或G1期同步化的大鼠表皮角质形成细胞原代单层培养物中的细胞接触双(2-氯乙基)硫醚时，对交联的形成和细胞毒性进行了比较。用溴化乙锭荧光测定法测量交联的剂量反应性形成，在细胞周期任一位置的细胞暴露后立即进行测定。暴露后24小时，处于G1期暴露的细胞中的交联水平未显著降低，且仍呈剂量依赖性。然而，在G1期暴露的细胞中交联出现大幅减少。DNA链间交联的形成似乎与芥子气的细胞毒性有关。
