AN IMPORTANT ROLE OF GENETICAL INSTABILITY IN RADIATION CARCINOGENESIS

辐射会在辐射后存活的细胞后代中诱导遗传不稳定。为了了解适应性反应在诱导遗传不稳定性中的作用，我们集中研究了辐射后存活细胞中新产生的延迟染色体畸变率。大多数延迟性染色体畸变由双着丝粒染色体组成，其中大多数染色体没有伴随片段。低剂量(2cGy)的预照射可使高剂量照射引起的延迟染色体畸变率降低40%(p&lt；0.01)。特别令人感兴趣的是，在有片段的染色体中观察到双着丝粒染色体的减少，而在没有片段的染色体中观察到双着丝粒染色体的减少(p&lt；0.004)。根据这些结果，我们认为辐射引起的迟发性染色体畸变的形成机制与直接诱发的染色体畸变的形成机制不同。为了进一步了解迟发性染色体畸变的形成机制，我们研究了非同源末端连接修复缺陷的SCID小鼠细胞的迟发性染色体畸变率。结果表明，在同等存活剂量下，SCID细胞对延迟染色体畸变率的形成比野生型细胞更为敏感，提示非同源末端连接修复在预防辐射引起的遗传不稳定性中可能起到一定作用。

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.