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长波紫外线辐射的旁观者效应通过诱导抗氧化防御来保护 A375 黑素瘤细胞。

Bystander effect of ultraviolet A radiation protects A375 melanoma cells by induction of antioxidant defense.

机构信息

Department of Biochemistry & Biophysics, University of Kalyani, Kalyani, India.

出版信息

J Environ Sci Health C Toxicol Carcinog. 2022;40(1):46-67. doi: 10.1080/26896583.2021.1994820. Epub 2021 Dec 13.

Abstract

Ultraviolet (UV) irradiated cells release factors that result in varied responses by non-irradiated cells via bystander effects (BE). The UV-BE is dependent on the cell types involved and on the wavelength of the radiation. Using conditioned medium from UVA-irradiated A375 human melanoma cells (UVA-CM), UVA-bystander response was evaluated on the viability of naïve A375 cells. UVA-CM treatment itself did not alter cell viability; however, UVA-CM treated bystander cells were more resistant to the lethal action of UVA, UVB, UVC or HO. Effects of UVA-CM on cell proliferation, mechanism of cell death, DNA damage, malondialdehyde formation, generation of reactive oxygen species (ROS) and antioxidant status were studied in A375 cells. We observed that UVA-CM triggered antioxidant defenses to elicit protective responses through elevation of antioxidant enzyme activities in cells, which persisted until 5 h after exposure to UVA-CM. This was possibly responsible for decreased generation of ROS and diminished DNA and membrane damage in cells. These bystander cells were resistant to killing when exposed to different genotoxic agents. Damaged nuclei, induction of apoptosis and autophagic death were also lowered in these cells. The influence of UVA-CM on cancer stem cells side population was assessed.Highlights:UVA radiation induced bystander effects in A375 cellsDamage by genotoxicants is suppressed due to lower ROS generation on UVA-CM treatmentUVA-CM exposure enhanced higher activities of CAT and GPxResistance to genotoxic agents in such cells was due to elevated antioxidant defenceUVA-bystander phenomenon was a protective response.

摘要

紫外线(UV)辐射的细胞会释放因子,通过旁观者效应(BE)导致非辐射细胞产生不同的反应。UV-BE 取决于所涉及的细胞类型和辐射的波长。使用 UVA 辐射的 A375 人黑色素瘤细胞(UVA-CM)的条件培养基,评估了 UVA 旁观者反应对幼稚 A375 细胞活力的影响。UVA-CM 处理本身不会改变细胞活力;然而,UVA-CM 处理的旁观者细胞对 UVA、UVB、UVC 或 HO 的致死作用更具抵抗力。研究了 UVA-CM 对 A375 细胞增殖、细胞死亡机制、DNA 损伤、丙二醛形成、活性氧(ROS)生成和抗氧化状态的影响。我们观察到,UVA-CM 通过提高细胞中抗氧化酶的活性来触发抗氧化防御,从而引发保护反应,这种反应一直持续到暴露于 UVA-CM 后 5 小时。这可能是由于 ROS 生成减少和细胞 DNA 和膜损伤减少所致。当这些旁观者细胞暴露于不同的遗传毒性剂时,它们具有抗杀伤性。受损的细胞核、细胞凋亡和自噬性死亡的诱导也降低了这些细胞。还评估了 UVA-CM 对癌症干细胞侧群的影响。

要点

UVA 辐射在 A375 细胞中诱导旁观者效应

由于 UVA-CM 处理时 ROS 生成减少,遗传毒性剂引起的损伤受到抑制

UVA-CM 暴露增强了 CAT 和 GPx 的更高活性

这些细胞对遗传毒性剂的抗性归因于升高的抗氧化防御

UVA 旁观者现象是一种保护反应。

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