Savage J R, Harvey A N
MRC Radiobiology Unit, Chilton, Didcot, U.K.
Mutat Res. 1991 Sep-Oct;250(1-2):307-17. doi: 10.1016/0027-5107(91)90186-r.
The controversy of the Classic versus the Exchange theories for the origin of simple chromatid breaks is outlined. Using BrdU harlequin sister-chromatid differentiation four Revell ratios can be defined and these have been obtained and tested as a block in V79 hamster cells. The values are quite different from the simple predictions. However, values similar to those observed (taken as a block) can be readily simulated from Revell theory by making the assumption that intra-chromatid events are dominant (0.7:0.3). They can also be obtained from contingency modelling of Classic theory using the same assumption plus the additional constraint that there is no contribution from isolated single lesions (Poisson class 1). If this latter assumption is correct, then the frequency of breaks involving a colour-jump (ratio III) should not decline to zero as the dose falls. A dose-response experiment shows that it does not, but remains approximately constant at about 12%, even in the unirradiated control. An added complication arises when we discover for the TB/BB situation, that whilst neither breaks nor gaps show any excess BB involvement (sensitisation), lesions involved in interchanges show at least a 2-fold BB excess. Clearly, the chromatid discontinuities we are scoring are not behaving as would be expected of a residue of unrejoined primary breaks (Classic theory) and we infer also that they are not 'simple'.
本文概述了关于简单染色单体断裂起源的经典理论与交换理论之间的争议。利用BrdU 花斑型姐妹染色单体分化技术,可以定义四个雷维尔比率,并且已经在V79仓鼠细胞中作为一个整体获得并测试了这些比率。这些值与简单预测有很大不同。然而,通过假设染色单体内事件占主导(0.7:0.3),可以很容易地从雷维尔理论模拟出与观察到的值(作为一个整体)相似的值。使用相同假设加上不存在孤立单损伤(泊松1类)的额外约束条件,也可以从经典理论的列联模型中得到这些值。如果后一个假设正确,那么随着剂量降低,涉及颜色跳跃的断裂频率(比率III)不应降至零。剂量反应实验表明并非如此,即使在未照射的对照中,该频率也保持在约12%左右大致恒定。当我们发现对于TB/BB情况,虽然断裂和间隙都没有显示出任何BB参与过多(敏化),但涉及互换的损伤显示出至少2倍的BB过量时,又出现了一个额外的复杂情况。显然,我们所计分的染色单体不连续性的行为并不像未连接的初级断裂残余物(经典理论)所预期的那样,我们还推断它们不是“简单的”。