Azzam E I, de Toledo S M, Gooding T, Little J B
Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Radiat Res. 1998 Nov;150(5):497-504.
We demonstrate by western analysis that the expression levels of TP53 (formerly known as p53), CDKN1A (formerly known as p21Waf1), CDC2 (formerly known as p34cdc2), CCNB1 (cyclin B1) and RAD51 are significantly modulated in confluent, density-inhibited human diploid cell populations exposed to doses where only a small fraction of the nuclei are actually traversed by an alpha-particle track. The extent of modulation of TP53 and CDKN1A is significantly reduced in the presence of the gap junction inhibitor lindane and in irradiated low-density cell populations. In situ immunofluorescence studies show that at doses where about 2% of the nuclei would be traversed by an alpha particle, induction of CDKN1A occurs in more cells than predicted. Furthermore, the induced cells are present in isolated aggregates of neighboring cells. Therefore, our studies at the gene expression level indicate that similar signaling pathways are induced in bystander cells that are not traversed by an alpha particle as in traversed cells, and that biological effects in cell populations are not restricted to the response of individual cells to the DNA damage they receive.
我们通过蛋白质免疫印迹分析证明，在汇合的、密度抑制的人二倍体细胞群体中，当暴露于仅一小部分细胞核实际被α粒子径迹穿过的剂量时，TP53（以前称为p53）、CDKN1A（以前称为p21Waf1）、CDC2（以前称为p34cdc2）、CCNB1（细胞周期蛋白B1）和RAD51的表达水平受到显著调节。在存在间隙连接抑制剂林丹的情况下以及在辐照的低密度细胞群体中，TP53和CDKN1A的调节程度显著降低。原位免疫荧光研究表明，在约2%的细胞核会被α粒子穿过的剂量下，CDKN1A的诱导发生在比预期更多的细胞中。此外，诱导的细胞存在于相邻细胞的孤立聚集体中。因此，我们在基因表达水平的研究表明，未被α粒子穿过的旁观者细胞中诱导的信号通路与被穿过的细胞相似，并且细胞群体中的生物学效应并不局限于单个细胞对其接收的DNA损伤的反应。
