芥子气对人皮肤细胞DNA交联形成与细胞毒性的关系

Relationship between Cutaneous Cytotoxicity and Formation of Interstrand DNA Cross links in Human Keratinocytes Caused by Sulfur Mustard

用不同剂量芥子气对单层人表皮基底细胞和人拟表皮染毒，观察诱发双链间ＤＮＡ交联的形成。结果表明在相同染毒剂量时，芥子气致人拟表皮ＤＮＡ交联形成率仅为单层人角朊细胞的１／４。染毒后１ｈ人角朊细胞ＤＮＡ交联形成率与染毒２４ｈ后比较明显降低。芥子气对皮肤细胞的ＤＮＡ交联作用与其细胞毒性作用之间存在有明显的剂量反应和时间反应关系。该种交联作用可能是芥子气导致皮肤细胞死亡的原因之一。芥子气对具有完整屏障结构的人拟表皮同样显示有致ＤＮＡ交联形成作用。

Epidermical basal keratinocytes are the major target in sulfur mustard induced cutaneous injury.Sulfur mustard in aqueous solution forms a cyclic sulphonium ion which ionizes to the carbonium.There is a possibility that those ions and two reactive chloroethyl groups of sulfur mustard allow the formation of cross links between guanine residues on the same or on opposite DNA strands.Interstrand DNA cross links was measured in monolayer human keratinocyte culture and in human pseudo epidermis immediately after exposure to sulfur mustard.The dose responsive increase in the interstrand DNA crosslinks was found in both DNA from human keratinocytes and human pseudo epidermis.Good correlation between dose responsive increase of interstrand DNA cross links and cutaneous cytotoxicity by sulfur mustard was found in this study.The study confirmed the formation of interstrand DNA cross links of human keratinocytes by sulfur mustard.The formation of interstrand DNA cross links in monolayer human keratinocytes was three times more than that in human pseudoepidermis under same exposure dose of sulfur mustard.The repair ability to DNA cross links was found in human pseudo epidermis.The percentage of DNA cross links in human pseudo epidermis at 0 hour after exposure to sulfur mustard was higher than that at 24 hours after exposure.The dose responsive and time responsive correlations were found between formation of DNA cross links and cytotoxicity in human keratinocytes after exposed to sulfur mustard.It is likely that formation of interstrand DNA cross links is related to the cytotoxicity of sulfur mustard.