Iliakis G, Wright E, Ngo F Q
Radiat Environ Biophys. 1987;26(1):47-62. doi: 10.1007/BF01211364.
C3H mouse 10 T1/2 cells showing strong inhibition of growth at confluency were grown under daily refeeding in the presence of BrdUrd (from 0 to 1 microM) and exposed to gamma-rays either while exponentially growing or in the plateau phase. An increase in radiosensitivity was observed in both growth conditions mainly reflected by a reduction in Dq. Greater radiosensitization was observed in exponentially growing than in plateau-phase cells, and 3-4 times higher BrdUrd concentrations were required in plateau-phase cells for similar potentiation in killing. This effect could not be entirely attributed to a reduction in BrdUrd incorporation since measurements with 3H-BrdUrd showed reductions in incorporation between only 17-47% in plateau-phase cells. The rate of repair of potentially lethal damage (PLD) as demonstrated by delayed plating was not affected by the incorporation of BrdUrd, but the amount of repair (measured as the relative increase in cell survival) was higher for BrdUrd-containing cells. Post-irradiation treatment of cells in the plateau-phase (no BrdUrd) with 9-beta-D-arabinofuranosyladenine (araA) caused fixation of radiation-induced PLD. AraA treatment of cells grown in the presence of various amounts of BrdUrd also caused fixation of PLD, but resulted in survival levels similar to those observed with cells growing in BrdUrd-free medium. This result indicates that BrdUrd mediated radiosensitization cannot be observed when cells are prevented from repairing PLD by postirradiation incubation with araA. Based on these findings we propose that the mechanism of radiosensitization by BrdUrd incorporation might be, by increasing probability of fixation, mediated by the postirradiation progression of cells through the cycle, of a sector of PLD also sensitive to post-irradiation treatment with araA. For this sector of PLD the term alpha-PLD has been proposed.
在汇合时显示出强烈生长抑制的C3H小鼠10 T1/2细胞，在每日重新喂食且存在BrdUrd（浓度从0到1 microM）的条件下培养，并在指数生长期或平台期时接受γ射线照射。在两种生长条件下均观察到放射敏感性增加，主要表现为Dq降低。指数生长期细胞比平台期细胞表现出更大的放射增敏作用，并且平台期细胞需要3 - 4倍更高浓度的BrdUrd才能达到类似的杀伤增强效果。这种效应不能完全归因于BrdUrd掺入量的减少，因为用³H - BrdUrd测量显示平台期细胞中掺入量仅减少17 - 47%。通过延迟接种所证明的潜在致死性损伤（PLD）的修复速率不受BrdUrd掺入的影响，但含BrdUrd细胞的修复量（以细胞存活的相对增加来衡量）更高。用9 - β - D - 阿拉伯呋喃糖基腺嘌呤（araA）对处于平台期（无BrdUrd）的细胞进行辐照后处理会导致辐射诱导的PLD固定。用araA处理在不同量BrdUrd存在下生长的细胞也会导致PLD固定，但存活水平与在无BrdUrd培养基中生长的细胞所观察到的相似。这一结果表明，当通过用araA进行辐照后孵育阻止细胞修复PLD时，无法观察到BrdUrd介导的放射增敏作用。基于这些发现，我们提出，通过BrdUrd掺入实现放射增敏的机制可能是，通过增加固定概率，由细胞在照射后通过细胞周期的进程介导，使一部分对araA辐照后处理也敏感的PLD得以固定。对于这部分PLD，已提出术语α - PLD。
