Ionizing Radiation-Induced Responses in Human Cells with Differing TP53 Status

Mirzayans, Razmik; Andrais, Bonnie; Scott, April; Wang, Ying W.; Murray, David

doi:10.3390/ijms141122409

Cited by 100 publications

(121 citation statements)

References 146 publications

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“…In our studies, we have reported findings using A549 cells, which is a lung epithelial cell line harboring wild-type p53 protein, and HeLa cells, a cervical carcinoma cell line which is p53 negative by virtue of expression of HCV E6 antigen which degrades p53 protein (supplementary material Fig. S1B) (Del Nagro et al, 2014;Mirzayans et al, 2013;Radha et al, 1999;Wrede et al, 1991). Our experiments (described above) established that BrdU-mediated direct DNA damage induces senescence in both HeLa and A549 cells, meaning that p53 is dispensable for induction of cellular senescence.…”

Section: P53 Is Not Essential For Inducing Cellular Senescencementioning

confidence: 99%

“…On average, treated cells were three to four times larger than untreated cells (40-100 mm versus 10-30 mm for control cells). Given that HeLa cells show extremely low or no expression of active p53 protein (Del Nagro et al, 2014;Matlashewski et al, 1986;Mirzayans et al, 2013), the effect of BrdU treatment on A549 cells, which expresses wildtype p53 protein (supplementary material Fig. S1B) was analyzed (Fig.…”

Section: Cellular Senescence Is An Outcome Of Direct Dna Damagementioning

confidence: 99%

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Temporally distinct roles of ATM and ROS in genotoxic-stress-dependent induction and maintenance of cellular senescence

Nair

Bagheri

Saini

2015

Journal of Cell Science

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Cells exposed to genotoxic stress induce cellular senescence through a DNA damage response (DDR) pathway regulated by ATM kinase and reactive oxygen species (ROS). Here, we show that the regulatory roles for ATM kinase and ROS differ during induction and maintenance of cellular senescence. Cells treated with different genotoxic agents were analyzed using specific pathway markers and inhibitors to determine that ATM kinase activation is directly proportional to the dose of the genotoxic stress and that senescence initiation is not dependent on ROS or the p53 status of cells. Cells in which ROS was quenched still activated ATM and initiated the DDR when insulted, and progressed normally to senescence. By contrast, maintenance of a viable senescent state required the presence of ROS as well as activated ATM. Inhibition or removal of either of the components caused cell death in senescent cells, through a deregulated ATM-ROS axis. Overall, our work demonstrates existence of an intricate temporal hierarchy between genotoxic stress, DDR and ROS in cellular senescence. Our model reports the existence of different stages of cellular senescence with distinct regulatory networks.

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Section: P53 Is Not Essential For Inducing Cellular Senescencementioning

confidence: 99%

Section: Cellular Senescence Is An Outcome Of Direct Dna Damagementioning

confidence: 99%

Temporally distinct roles of ATM and ROS in genotoxic-stress-dependent induction and maintenance of cellular senescence

Nair

Bagheri

Saini

2015

Journal of Cell Science

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“…Por todo ello, es aconsejable limitar estos procedimientos diagnósticos en los pacientes con SLF (9,10). En la paciente de nuestro caso clínico, tal vez deberíamos haber tenido más en cuenta esta circunstancia especial, ya que desde su diagnós-tico ha sido sometida a numerosas pruebas de imagen que suponían un extra de irradiación: TAC, PET, mamografías, radiografías simples.…”

Section: Tabla III Li Fraumeni-like (Lfl): Criterios Diagnósticos Clíunclassified

Tumoración pélvica en una paciente con síndrome de Li Fraumeni

Baquedano

Campo

Octavio

et al. 2014

Rev. chil. obstet. ginecol.

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RESUMENEl síndrome de Li Fraumeni (SLF) es una rara enfermedad hereditaria asociada con un riesgo incrementado de padecer ciertos tumores malignos. Presentamos el caso de una paciente con diagnóstico de SLF con antecedentes de sarcoma de glúteo con metástasis pulmonares y cáncer de mama bilateral metacrónico. Acudió al Servicio de Urgencias por distensión y dolor abdominal. Se objetivó una masa pélvica y se pensó en un probable origen ovárico de la misma. La paciente fue intervenida en el Servicio de Ginecología, y durante la intervención se descartó dicho origen ya que la tumoración dependía del epiplón. El diagnóstico final fue metástasis de sarcoma. PALABRAS CLAVE: Síndrome de Li Fraumeni, Li Fraumeni like, TP53 SUMMARYLi-Fraumeni syndrome (LFS) is a rare, inherited syndrome associated with increased risk of various malignant tumors. We present the case of a patient diagnosed LSF with a history of gluteal sarcoma with lung metastases and metachronous bilateral breast cáncer. She came to the emergency department for abdominal bloating and pain. She had a pelvic mass and we had thought probable ovarian dependence. The patient was operated on at the Department of Gynecology, and during the intervention we realized that the tumor depended on the omentum. The final diagnosis was a metastatic of sarcoma. KEY WORD: Li Fraumeni syndrome, Li Fraumeni like syndrome, TP53 INTRODUCCIÓNEl síndrome de Li Fraumeni (SLF) es una enfermedad rara que se caracteriza por la aparición precoz de múltiples tumores malignos en un individuo que pueden debutar desde la infancia hasta la edad adulta (1). Existen dos formas clínicas: el Li Fraumeni clásico y el Li Fraumeni-like (LFL), este último con criterios menos restrictivos al momento del diagnóstico (2,3). Se hereda con carácter autosómico dominante con penetrancia incompleta, que está condicionada en el 70% de los casos por mutaciones de la línea germinal del gen TP53.Los tumores más frecuentemente implicados en este síndrome son los sarcomas de partes blandas y osteosarcomas, cáncer de mama en mujeres 182 REV CHIL OBSTET GINECOL 2014; 79(3): 182 -186

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“…The p21 and p53 genes are important for cell responses front to the DNA damage processes and apoptosis induction (Mirzayans et al, 2013). Apoptosis has an important role in the homeostasis as well regulation of apoptosis levels related to the prevention of diseases and may be an indicative of genotoxic stress.…”

Section: Nuclear Changes Induced By Occupational Exposure To Ir In Ormentioning

confidence: 99%

Toxicogenetic biomonitoring of occupational risk induced by ionizing radiation

Ronald¹,

Torequl²,

Ricardo³

et al. 2016

Afr. J. Pharm. Pharmacol.

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Occupational exposure to ionizing radiation (IR) can cause systemic acute and chronic effects on human health, including genetic instability that may be etiology of various diseases, including cancer. The aim of this study was to evaluate the possible toxicogenetic changes in haematological and biochemical parameters, and cytogenetic biomarkers (micronuclei and nuclear abnormalities) indicators of mutagenicity and apoptosis, as well as seek their correlation with lifestyle, age and gender. In accordance with the ethical aspects, 45 professionals (technicians and technologists in radiology) occupationally exposed to low doses of IR participated in this study. For control, 45 healthy individuals were not exposed to IR and/or genotoxic chemicals were included. Peripheral blood and oral epithelium samples were used in the toxic evaluations. The results suggested unchanged hematological biomarkers but a significant (P < 0.05) increases in the frequency of micronuclei, sprouts, binucleate cells and bridges, as well as karyolysis and karyorrhexis in professional radiology sector. Hepatic and nephritic toxicity were not observed. Without protection, a significant (P < 0.01) correlation (P < 0.05) was observed between toxicogenetic biomarkers with age, smoking, alcohol consumption, time and place of work. In conclusion, IR may be associated with genetic instability in health diseases, like cancer.

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Ionizing Radiation-Induced Responses in Human Cells with Differing TP53 Status

Cited by 100 publications

References 146 publications

Temporally distinct roles of ATM and ROS in genotoxic-stress-dependent induction and maintenance of cellular senescence

Temporally distinct roles of ATM and ROS in genotoxic-stress-dependent induction and maintenance of cellular senescence

Tumoración pélvica en una paciente con síndrome de Li Fraumeni

Toxicogenetic biomonitoring of occupational risk induced by ionizing radiation

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