Cohen L F, Kraemer K H, Waters H L, Kohn K W, Glaubiger D L
Mutat Res. 1981 Feb;80(2):347-56. doi: 10.1016/0027-5107(81)90107-x.
8-Methoxypsoralen (8-MOP) when irradiated with long wavelength ultraviolet radiation (UV-A) inhibits DNA synthesis in lymphocytes in vitro and in vivo. 8-MOP binds reversibly to DNA in the dark; when exposed to UV-A, covalent monoadducts and cross-links are formed with the DNA. The present study correlates the cytotoxic effects of 8-MOP plus UV-A with DNA crosslinking. E-B virus transformed human lymphoblastoid cells were suspended in a colorless salt solution containing 8-MOP and exposed to UV-A from fluorescent lamps filtered to remove radiation below 320 nm (22.5 J/m2-sec). Cells were then returned to complete medium and assayed for survival (by daily counts of viable cells and by cloning in microtiter wells) and for DNA crosslinking by alkaline elution. 8-MOP alone or UV-A alone resulted in minimal to no alterations in survival or in DNA crosslinking. DNA crosslinking was found to be linearly dependent on 8-MOP concentration (in the range of 0.01-1.0 microgram/ml) for 3 different UV-A doses (3000-15 000 J/m2). The surviving fraction declined exponentially as a function of the relative number of DNA crosslinks. These results suggest that the cytotoxic effects of photoactivated 8-MOP in human lymphoblastoid cells may depend on DNA interstrand crosslinks.
8-甲氧基补骨脂素（8-MOP）在受到长波长紫外线辐射（UV-A）照射时，可在体外和体内抑制淋巴细胞中的DNA合成。8-MOP在黑暗中与DNA可逆性结合；当暴露于UV-A时，会与DNA形成共价单加合物和交联。本研究将8-MOP加UV-A的细胞毒性作用与DNA交联相关联。将EB病毒转化的人淋巴母细胞悬浮于含有8-MOP的无色盐溶液中，并暴露于经滤光以去除波长低于320nm辐射的荧光灯发出的UV-A（22.5J/m2·秒）下。然后将细胞放回完全培养基中，检测其存活率（通过每日计数活细胞和在微量滴定孔中克隆）以及通过碱性洗脱检测DNA交联情况。单独使用8-MOP或单独使用UV-A对存活率或DNA交联的影响极小或无影响。对于3种不同的UV-A剂量（3000-15000J/m2），发现DNA交联与8-MOP浓度（在0.01-1.0微克/毫升范围内）呈线性相关。存活分数随DNA交联相对数量呈指数下降。这些结果表明，光活化的8-MOP对人淋巴母细胞的细胞毒性作用可能取决于DNA链间交联。
