AN IMPORTANT ROLE OF GENETICAL INSTABILITY IN RADIATION CARCINOGENESIS

辐射会在存活细胞的后代中引起遗传不稳定。为了了解适应性反应对诱导遗传不稳定性的影响，我们重点研究了辐照后存活细胞30代以上新产生的延迟性染色体畸变。大多数延迟性染色体畸变由双中心染色体组成，其中大多数不伴有片段。低剂量（2 cGy）预照射可使高剂量所致延迟性染色体畸变发生率降低40% （p<0.01）。特别有趣的是，在那些有片段的人身上观察到双中心染色体的减少，而在那些没有片段的人身上却没有（p<0.004）。根据这些结果，我们认为辐射延迟性染色体畸变的形成机制不同于直接诱导的染色体畸变。为了进一步了解延迟型畸变的形成机制，我们研究了非同源末端连接修复缺陷的scid小鼠细胞的延迟型染色体畸变。结果表明，scid细胞在同等存活剂量下对延迟染色体畸变的形成比野生型细胞更敏感，提示非同源末端连接修复可能在预防辐射引起的遗传不稳定中起作用。

Radiation induces genetic instability in the progeny of cells that survive irradiation. To know the effect of adaptive response on the induction of genetic instability, we focused our study on delayed chromosome aberrations newly produced in surviving cells over 30 cell generations post-irradiation. Most of the delayed chromosome aberrations consists of dicentric chromosomes, where the majority of them is not accompanied with a fragment. Pre-irradiation of a low dose (2 cGy) results in 40% reduction (p<0.01) of the frequency of the delayed chromosome aberrations induced by a high-dose irradiation. Of particular interest is that reduction of dicentric chromosomes is observed in those with a fragment but not in those without a fragment (p<0.004). From these results, we purpose that the mechanism of the formation of the delayed chromosome aberrations by radiation is different from that of directly induced chromosome aberrations. To know the mechanism of the formation of the delayed-type aberrations further, we studied the delayed chromosome aberrations in scid mouse cells which defect in non-homologous end joining repair. The result shows that scid cells are more sensitive to the formation of the delayed chromosome aberrations than wild-type cells when they are exposed to an equivalent surviving dose, suggesting that non-homologous end joining repair may play a role in prevention of genetic instability by radiation.