Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON, Canada.
Int J Radiat Biol. 2011 Nov;87(11):1120-5. doi: 10.3109/09553002.2011.610866.
A number of contradictory studies have reported a role or not for p53 (protein 53) in the production of radiation-induced bystander effects. Most of these studies looked at a range of cell lines with normal or compromised p53 function.
In this study, Human Colon Tumour line 116 (HCT 116) cells with confirmed wild type p53 function and a corresponding p53 null HCT 116 line were used to test for bystander signal production and response to bystander signals in a mix/match protocol using the medium transfer technique.
The results showed that both the null cells and the wild type cells produced bystander signals. However, only the p53 wild type cells responded to signals from either cell line. The Human Papilloma Virus transfected keratinocyte line G (HPV-G) reporter cell line used routinely in our laboratory was used to confirm that the null cells were producing signals.
We conclude that in this system the p53 pathway is involved in response of cells to bystander signals but that signals can be produced by cells which do not have functional p53. If these results apply in vivo, they could be important in radiotherapy where tumours may have compromised p53 function but surrounding (and distant) normal tissue may have wild type functional p53.
许多相互矛盾的研究报告表明,p53(蛋白 53)在辐射诱导的旁观者效应的产生中发挥作用或不发挥作用。这些研究大多观察了一系列具有正常或受损 p53 功能的细胞系。
在这项研究中,使用经证实具有野生型 p53 功能的人结肠肿瘤细胞系 116(HCT 116)和相应的 p53 缺失 HCT 116 系,通过使用培养基转移技术的混合/匹配方案,测试旁观者信号的产生和对旁观者信号的反应。
结果表明,缺失细胞和野生型细胞都产生了旁观者信号。然而,只有 p53 野生型细胞对来自任一细胞系的信号做出反应。我们实验室常规使用的人乳头瘤病毒转染角质形成细胞系 G(HPV-G)报告细胞系用于证实缺失细胞正在产生信号。
我们得出结论,在这个系统中,p53 途径参与了细胞对旁观者信号的反应,但信号可以由不具有功能性 p53 的细胞产生。如果这些结果在体内适用,它们可能在放射治疗中很重要,因为肿瘤可能具有受损的 p53 功能,但周围(和远处)正常组织可能具有野生型功能性 p53。