Intercellular communication is involved in the bystander regulation of gene expression in human cells exposed to very low fluences of alpha particles
Intercellular communication is involved in the bystander regulation of gene expression in human cells exposed to very low fluences of alpha particles
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DOI：
10.2307/3579865
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发表时间：
1998-11-01
影响因子：
3.4
通讯作者：
Little, JB
中科院分区：
文献类型：
--
作者：
Azzam, EI;de Toledo, SM;Little, JB
我们通过Western分析证明，在融合的、密度抑制的人类二倍体细胞群体中，TP53(以前称为p53)、CDKN1A(以前称为p21(Waf1))、CDC2(以前称为p34(Cdc2))、CCNB1(细胞周期蛋白B1)和RAD51的表达水平受到显著调节，其中只有一小部分细胞核实际上被α粒子轨迹穿过。在缝隙连接抑制剂林丹的存在和照射的低密度细胞群中，TP53和CDKN1A的调制程度显著降低。原位免疫荧光研究表明，在约2%的细胞核被a粒子穿过的剂量下，CDKN1A的诱导在更多的细胞中发生，比预期的要多。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上的研究表明，在没有被α粒子穿越的旁观者细胞中诱导了类似的信号通路，并且细胞群体中的生物效应并不局限于单个细胞对它们受到的DNA损伤的反应。(C)1998年，由辐射研究学会提供。
We demonstrate by western analysis that the expression levels of TP53 (formerly known as p53), CDKN1A (formerly known as p21(Waf1)), CDC2 (formerly known as p34(cdc2)), 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 a 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. (C) 1998 by Radiation Research Society.