Abstract：
Sulfur mustard (SM), a chemical warfare agent, can form adducts with DNA, RNA, and proteins. Reactions with DNA lead to the formation of both DNA monoadducts and interstrand cross-links, resulting in DNA damage, and is an important component of SM toxicity. Our previous in vivo studies indicated that dividing cells such as hematopoietic stem cells and intestinal villi stem cells seemed to have increased sensitivity to SM. Therefore, to compare the sensitivity of somatic and stem cells to SM and to investigate the mechanism of SM cytotoxicity, we isolated human foreskin fibroblasts, reprogrammed them into pluripotent stem cells, and then compared the DNA damage repair pathways involved upon SM treatment. Our results indicated that proliferating stem cells were more sensitive to SM-induced DNA damage, and the damage mainly comprised single-stranded breaks. Furthermore, the pathways involved in DNA repair in stem cells and somatic cells were different.
摘要：
硫芥末（SM），化学战剂，可以与DNA形成加合物，RNA,和蛋白质。与DNA的反应导致DNA单加合物和链间交联的形成，导致DNA损伤,是SM毒性的重要构成部门。我们先前的体内研究表明，分裂细胞，例如造血干细胞和肠绒毛干细胞似乎对SM的敏感性增加。因此,为了比较体细胞和干细胞对SM的敏感性，并研究SM的细胞毒性机制，我们分离了人包皮成纤维细胞，将它们重新编程为多能干细胞，然后比较SM治疗涉及的DNA损伤修复途径。我们的结果表明，增殖干细胞对SM诱导的DNA损伤更敏感，损害主要包括单股断裂。此外，干细胞和体细胞参与DNA修复的途径不同。
