AN IMPORTANT ROLE OF GENETICAL INSTABILITY IN RADIATION CARCINOGENESIS

辐射会引起辐射后存活的细胞后代的遗传不稳定性。为了了解适应性反应对诱导遗传不稳定性的影响，我们将研究重点放在照射后30代以上存活细胞中新产生的延迟染色体畸变上。大多数迟发性染色体畸变由双着丝粒染色体组成，其中大多数不伴有片段。低剂量（2cGy）预照射可使高剂量照射诱发的迟发性染色体畸变率降低40%（p<0.01）。特别有趣的是，在有片段的那些中观察到双着丝粒染色体减少，而在没有片段的那些中没有观察到双着丝粒染色体减少（p<0.004）。由此，我们认为辐射诱发的迟发性染色体畸变的形成机制不同于直接诱发的染色体畸变。为了进一步了解迟发型畸变的形成机制，我们对scid小鼠细胞中非同源末端连接修复缺陷的迟发型染色体畸变进行了研究。结果表明，scid细胞在同等剂量照射下比野生型细胞更易发生迟发性染色体畸变，提示非同源末端连接修复可能在防止辐射引起的遗传不稳定性中发挥作用。

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.