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旁观者效应诱导体外培养的小鼠膀胱细胞凋亡相关蛋白变化及终末分化。

Bystander effect induced changes in apoptosis related proteins and terminal differentiation in in vitro murine bladder cultures.

作者信息

Vines A M, Lyng F M, McClean B, Seymour C, Mothersill C E

机构信息

Radiation and Environmental Science Centre, Focas Institute, Dublin Institute of Technology, Dublin.

出版信息

Int J Radiat Biol. 2009 Jan;85(1):48-56. doi: 10.1080/09553000802635047.

DOI:10.1080/09553000802635047
PMID:19205984
Abstract

PURPOSE

Radiation-induced bystander effects are now an established phenomenon seen in numerous cell and tissue culture models. The aim of this investigation was to examine the bystander signal and response in a multicellular primary tissue culture system in vitro.

METHODS AND MATERIALS

Murine bladder samples were explanted and directly exposed to gamma radiation, or treated with irradiated tissue conditioned medium (ITCM) generated from the directly irradiated cultures.

RESULTS

Results indicated that there was a strong bystander signal produced by the tissue that caused both dose-dependent and -independent changes in the ITCM treated tissue. Significantly increased B-cell lymphoma 2 (Bcl2) expression was noted after treatment with 0.5Gy and 5Gy ITCM (approximately 80%), while dose-dependent changes were observed in c-myelocytomatosis (cMyc) (39.48% at 0.5 Gy ITCM, 81.28% at 5 Gy ITCM) and the terminal differentiation marker uroplakin III (17.88% at 0.5 Gy). Nuclear fragmentation was also significantly increased at both doses of ITCM.

CONCLUSION

These data suggest that the bystander signal produced in a multicellular environment induces complex changes in the ITCM-treated culture, and that these changes are reflective of a coordinated response to maintain integrity throughout the tissue.

摘要

目的

辐射诱导的旁观者效应现已成为众多细胞和组织培养模型中公认的现象。本研究的目的是在体外多细胞原代组织培养系统中检测旁观者信号和反应。

方法和材料

将小鼠膀胱样本取出并直接暴露于伽马辐射,或用直接照射培养物产生的辐照组织条件培养基(ITCM)处理。

结果

结果表明,组织产生了强烈的旁观者信号,导致ITCM处理的组织发生剂量依赖性和非依赖性变化。用0.5Gy和5Gy ITCM处理后,B细胞淋巴瘤2(Bcl2)表达显著增加(约80%),而c-髓细胞瘤病(cMyc)(0.5Gy ITCM时为39.48%,5Gy ITCM时为81.28%)和终末分化标志物uroplakin III(0.5Gy时为17.88%)出现剂量依赖性变化。两种剂量的ITCM处理后核碎裂也显著增加。

结论

这些数据表明,在多细胞环境中产生的旁观者信号在ITCM处理的培养物中诱导复杂变化,并且这些变化反映了维持整个组织完整性的协调反应。

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