Age-dependent effects on radiation-induced carcinogenesis in the rat thyroid

AbstractChildhood radiation exposure is a known thyroid cancer risk factor. This study evaluated the effects of age on radiation-induced thyroid carcinogenesis in rats irradiated with 8 Gy X-rays. We analyzed cell proliferation, cell death, DNA damage response, and autophagy-related markers in 4-week-old (4W) and 7-month-old (7M) rats and the incidence of thyroid tumors in 4W, 4-month-old (4M), and 7M rats 18 months after irradiation. Cell death and DNA damage response were increased in 4W rats compared to those in controls at 1 month post-irradiation. More Ki-67-positive cells were observed in 4W rats at 12 months post-irradiation. Thyroid tumors were confirmed in 61.9% (13/21), 63.6% (7/11), and 33.3% (2/6) of irradiated 4W, 4M, and 7M rats, respectively, compared to 0%, 14.3% (1/7), and 16.7% (1/6) in the respective nonirradiated controls. There were 29, 9, and 2 tumors in irradiated 4W, 4M, and 7M rats, respectively. The expression of several autophagy components was downregulated in the area surrounding radiation-induced thyroid carcinomas in 4W and 7M rats. LC3 and p62 expression levels decreased in radiation-induced follicular carcinoma in 4W rats. Radiosensitive cells causing thyroid tumors may be more prevalent in young rats, and abrogation of autophagy may be associated with radiation-induced thyroid carcinogenesis.

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Depletion of the DarG antitoxin in Mycobacterium tuberculosis triggers the DNA‐damage response and leads to cell death

Molecular Microbiology ◽

10.1111/mmi.14571 ◽

2020 ◽

Vol 114 (4) ◽

pp. 641-652 ◽

Cited By ~ 1

Author(s):

Anisha Zaveri ◽

Ruojun Wang ◽

Laure Botella ◽

Ritu Sharma ◽

Linnan Zhu ◽

...

Keyword(s):

Dna Damage ◽

Cell Death ◽

Mycobacterium Tuberculosis ◽

Dna Damage Response ◽

Damage Response

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Punicalagin from pomegranate promotes human papillary thyroid carcinoma BCPAP cell death by triggering ATM-mediated DNA damage response

Nutrition Research ◽

10.1016/j.nutres.2017.09.001 ◽

2017 ◽

Vol 47 ◽

pp. 63-71 ◽

Cited By ~ 9

Author(s):

Xin Yao ◽

Xian Cheng ◽

Li Zhang ◽

Huixin Yu ◽

Jiandong Bao ◽

...

Keyword(s):

Dna Damage ◽

Cell Death ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Dna Damage Response ◽

Papillary Thyroid ◽

Damage Response

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RUNX Family Participates in the Regulation of p53-Dependent DNA Damage Response

International Journal of Genomics ◽

10.1155/2013/271347 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 22

Author(s):

Toshinori Ozaki ◽

Akira Nakagawara ◽

Hiroki Nagase

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Cell Death ◽

Cell Cycle Arrest ◽

Dna Damage Response ◽

Apoptotic Cell ◽

Genetic Alterations ◽

Apoptotic Cell Death ◽

Cycle Arrest ◽

Damage Response

A proper DNA damage response (DDR), which monitors and maintains the genomic integrity, has been considered to be a critical barrier against genetic alterations to prevent tumor initiation and progression. The representative tumor suppressor p53 plays an important role in the regulation of DNA damage response. When cells receive DNA damage, p53 is quickly activated and induces cell cycle arrest and/or apoptotic cell death through transactivating its target genes implicated in the promotion of cell cycle arrest and/or apoptotic cell death such asp21WAF1,BAX, andPUMA. Accumulating evidence strongly suggests that DNA damage-mediated activation as well as induction of p53 is regulated by posttranslational modifications and also by protein-protein interaction. Loss of p53 activity confers growth advantage and ensures survival in cancer cells by inhibiting apoptotic response required for tumor suppression. RUNX family, which is composed of RUNX1, RUNX2, and RUNX3, is a sequence-specific transcription factor and is closely involved in a variety of cellular processes including development, differentiation, and/or tumorigenesis. In this review, we describe a background of p53 and a functional collaboration between p53 and RUNX family in response to DNA damage.

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