Brown J M, Kovacs M S
Department of Radiation Oncology, Stanford University School of Medicine, California 94305.
Radiat Res. 1993 Oct;136(1):71-6.
A long-standing controversy in radiation cytogenetics is the precise mechanism for the formation of chromosome exchanges. The classical breakage-and-reunion hypothesis suggested by Stadler and developed by Sax was challenged in 1959 by Revell, who proposed that radiation produced an "unstable lesion" which could interact with another such lesion to form an exchange. A difference between the predictions of these two theories is that the breakage-and-reunion hypothesis would allow the two broken ends of a chromosome to join with contemporary broken ends in different chromosomes, thereby producing nonreciprocal exchanges involving more than two chromosomes. This would not occur according to the Revell theory, which demands pairwise commital to the exchange. The ability to "paint" a whole chromosome using fluorescence in situ hybridization allows a discrimination between reciprocal and nonreciprocal chromosome exchanges. We scored metaphases in AG1522 human fibroblasts irradiated in G1 phase with 6 Gy and hybridized to chromosomes 1, 4, or 8. Of the complete exchanges involving one of these chromosomes, 26% were found to possess either one or three centromeres in the exchange pair. Since we could rule out any significant contribution of complex exchanges (i.e., those involving more than one break per chromosome), these one- and three-centromere exchange pairs must have arisen from a nonreciprocal exchange. Because an equal number of nonreciprocal exchanges would be expected to have a total of two centromeres, this suggests that approximately 50% of all exchanges at this dose were nonreciprocal. These data support the breakage-and-reunion hypothesis and are incompatible with the standard form of the exchange hypothesis of Revell.
辐射细胞遗传学中一个长期存在的争议是染色体交换形成的确切机制。由斯塔德勒提出并由萨克斯进一步发展的经典断裂重接假说是1959年由雷维尔提出挑战的，雷维尔提出辐射产生一种“不稳定损伤”，它可以与另一种这样的损伤相互作用形成交换。这两种理论预测的一个差异是，断裂重接假说将允许一条染色体的两个断裂末端与不同染色体上同时期的断裂末端连接，从而产生涉及两条以上染色体的非相互交换。根据雷维尔理论，这种情况不会发生，该理论要求交换是成对进行的。利用荧光原位杂交“描绘”整条染色体的能力使得能够区分相互和非相互染色体交换。我们对处于G1期、接受6戈瑞照射的AG1522人成纤维细胞的中期进行评分，并与1号、4号或8号染色体杂交。在涉及这些染色体之一的完全交换中，发现26%的交换对在交换中有一个或三个着丝粒。由于我们可以排除复杂交换（即每条染色体涉及一个以上断裂的交换）的任何显著贡献，这些一个和三个着丝粒的交换对一定是由非相互交换产生的。因为预计相等数量的非相互交换总共会有两个着丝粒，这表明在这个剂量下所有交换中约50%是非相互的。这些数据支持断裂重接假说，并且与雷维尔交换假说的标准形式不相容。
