Tumor Cell-Accelerated Senescence Is Associated With DNA-PKcs Status and Telomere Dysfunction Induced by Radiation

Dose-response : a Publication of International Hormesis Society
Miaomiao ZhangWenjian Li

Abstract

Whether telomere structure integrity is related to radiosensitivity is not well investigated thus far. In this study, we investigated the relation between telomere instability and radiation-induced accelerated senescence. Partial knockdown of DNA-dependent catalytic subunit of protein kinase (DNA-PKcs) in human breast cancer cell line MCF-7 was established by small interfering RNA. Radiosensitivity of control and DNA-PKcs knockdown MCF-7 cells was analyzed by clonogenetic assay. Cell growth was measured by real-time cell electronic sensing. Senescence and apoptosis were evaluated by β-galactosidase histochemical staining and fluorescence-activated cell sorting, respectively. DNA damage was determined by long polymerase chain reaction (PCR). Telomere length and integrity were analyzed by real-time PCR and cytogenetic assay, respectively. DNA-PKcs knockdown MCF-7 cells were more sensitive to X-irradiation than control cells. Further investigation revealed that accelerated senescence is more pronounced than apoptosis in cells after radiation, particularly in DNA-PKcs knockdown cells. The cytogenetic assay and kinetics of DNA damage repair revealed that the role of telomere end-capping in DNA-PKcs, rather than DNA damage repair, wa...Continue Reading

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Citations

Jan 29, 2020·Cellular & Molecular Biology Letters·Jiangdong SuiBenjamin P C Chen
Sep 6, 2020·Biomolecules·Xiaoyun Tang, David N Brindley
Jul 11, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Krishna N MishraGhazi A Alsbeih

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Methods Mentioned

BETA
transfection
fluorescence-activated cell sorting
X-ray
PCR
transfections
cytogenetic aberrations

Software Mentioned

Flowjo
RT
QuantiScan
CES

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis