酸性环境中辐射后的细胞周期进程与细胞凋亡

Cell cycle progression and apoptosis after irradiation in an acidic environment.

作者信息

Park H J, Lyons J C, Ohtsubo T, Song C W

机构信息

University of Minnesota Medical School, Department of Therapeutic Radiology-Radiation Oncology, Radiation Biology Section, 420 Delaware St. S.E., Box 494 Mayo, Minneapolis, MN 55455, USA.

出版信息

Cell Death Differ. 2000 Aug;7(8):729-38. doi: 10.1038/sj.cdd.4400702.

DOI:10.1038/sj.cdd.4400702

PMID:10918447

Abstract

We investigated the effect of an acidic environment on the radiation-induced G2/M arrest and apoptosis using RKO.C human colorectal cancer cells expressing wild-type p53 and RC10.1 cells, a subline of RKO.C cells deficient in p53 as well as p53+/+ MEFs and p53-/- MEFs (mouse embryonic fibroblasts). The cells were irradiated with 4 Gy or 12 Gy of gamma-rays in pH 7.5 medium or pH 6.6 medium. p53 accentuated the progression of cells from radiation-induced G2/M arrest to apoptosis and the pH 6.6 environment suppressed the progression of cells through G2/M-phase to apoptosis after irradiation. Further analysis indicated that the radiation-induced G2/M arrest was due mainly to G2 arrest in both pH 7.5 and pH 6.6. Therefore, it was concluded that p53 enhances, and an acidic environment suppresses, the exit of cells from radiation-induced G2 arrest by altering cyclin B1-Cdc2 kinase activity.

摘要

我们使用表达野生型p53的RKO.C人结肠癌细胞、RKO.C细胞的一个p53缺陷亚系RC10.1细胞以及p53+/+ MEF和p53-/- MEF（小鼠胚胎成纤维细胞），研究了酸性环境对辐射诱导的G2/M期阻滞和细胞凋亡的影响。将细胞在pH 7.5培养基或pH 6.6培养基中用4 Gy或12 Gy的γ射线进行照射。p53促进了细胞从辐射诱导的G2/M期阻滞向细胞凋亡的进展，并且pH 6.6环境抑制了照射后细胞通过G2/M期向细胞凋亡的进展。进一步分析表明，辐射诱导的G2/M期阻滞在pH 7.5和pH 6.6条件下主要是由于G2期阻滞。因此，得出结论：p53通过改变细胞周期蛋白B1-Cdc2激酶活性来增强，而酸性环境抑制细胞从辐射诱导的G2期阻滞中退出。