Grdina D J, Nagy B
Br J Cancer. 1986 Dec;54(6):933-41. doi: 10.1038/bjc.1986.264.
The radioprotector 2-[(aminopropyl)amino] ethanethiol (WR1065) was investigated with respect to its ability to affect radiation-induced DNA damage and repair in V79 cells. Studies were performed to evaluate the protector under conditions in which it is known to be effective in reducing the cytotoxic and mutagenic effects of gamma-irradiation. At a concentration of 4 mM, WR1065 protected against the formation of single strand breaks (SSB), as determined by the method of alkaline elution, when it was present during irradiation. The protector appeared, however, to inhibit the subsequent postirradiation repair or rejoining of SSB. While repair was complete within 24 h, the protector reduced the rate of repair by a factor of 3. This inhibitory effect on the rate of repair did not correlate with either measured differences in cell survival or mutagenesis. The radioprotector was also investigated with respect to its ability to affect cell cycle progression. WR1065 present in the growth medium inhibited the progression of cells through S-phase, and cell-doubling time following a 3 h exposure to the protector was increased from 11 to 18 h. These data are consistent with the well characterized property of thiols to inhibit DNA polymerase activity. It was concluded that, while the presence of WR1065 during irradiation reduced SSB-DNA damage, its effect on the subsequent rejoining of these breaks could not be correlated with its observed effect on protecting against radiation-induced mutagenesis. It may be that the inhibition of cell-cycle progression by the protector allowed more time to enhance the fidelity of repair as measured by the protector's ability to protect against radiation-induced mutagenesis.
对辐射防护剂2-[(氨丙基)氨基]乙硫醇（WR1065）影响V79细胞辐射诱导的DNA损伤和修复的能力进行了研究。开展了多项研究，以评估该防护剂在已知可有效降低γ射线辐照的细胞毒性和诱变效应的条件下的作用。通过碱性洗脱法测定，当WR1065在辐照期间存在时，4 mM浓度的该防护剂可防止单链断裂（SSB）的形成。然而，该防护剂似乎抑制了辐照后SSB的后续修复或重新连接。虽然修复在24小时内完成，但该防护剂使修复速率降低了三分之一。这种对修复速率的抑制作用与细胞存活或诱变的测量差异均无关联。还研究了该辐射防护剂影响细胞周期进程的能力。生长培养基中存在的WR1065抑制细胞通过S期的进程，在接触该防护剂3小时后，细胞倍增时间从11小时增加到18小时。这些数据与硫醇抑制DNA聚合酶活性的已充分表征的特性一致。得出的结论是，虽然辐照期间WR1065的存在减少了SSB-DNA损伤，但其对这些断裂后续重新连接的影响与观察到的其对防止辐射诱导诱变的保护作用无关。可能是该防护剂对细胞周期进程的抑制作用使得有更多时间提高修复的保真度，这可通过该防护剂防止辐射诱导诱变的能力来衡量。
