Age-dependent Effects on Radiation-induced Carcinogenesis in the Rat Thyroid

Overview

Journal Sci Rep

Specialty Science

Date 2021 Sep 28

PMID 34580369

Citations 4

Authors

Mutsumi Matsuu-Matsuyama

Kazuko Shichijo

Katsuya Matsuda

Nariaki Fujimoto

Hisayoshi Kondo

Shiro Miura

Tomomi Kurashige

Yuji Nagayama

Masahiro Nakashima

Affiliations

Soon will be listed here.

Abstract

Childhood 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.

Citing Articles

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Radiation makes cells select the form of death dependent on external or internal exposure: apoptosis or pyroptosis.

Shichijo K, Takatsuji T, Uzbekov D, Chaizhunusova N, Shabdarbaeva D, Kurisu M Sci Rep. 2023; 13(1):12002.

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References

Christov K . Radiation-induced thyroid tumors in infant rats. Radiat Res. 1978; 73(2):330-9. View

Kongara S, Karantza V . The interplay between autophagy and ROS in tumorigenesis. Front Oncol. 2012; 2:171. PMC: 3502876. DOI: 10.3389/fonc.2012.00171. View

Tanida I, Ueno T, Kominami E . LC3 and Autophagy. Methods Mol Biol. 2008; 445:77-88. DOI: 10.1007/978-1-59745-157-4_4. View

Takano T . Natural history of thyroid cancer [Review]. Endocr J. 2017; 64(3):237-244. DOI: 10.1507/endocrj.EJ17-0026. View

Bang H, Choi M, Kim C, Choi S . Gene expression profiling in undifferentiated thyroid carcinoma induced by high-dose radiation. J Radiat Res. 2016; 57(3):238-49. PMC: 4915541. DOI: 10.1093/jrr/rrw002. View

Ernest N, Habela C, Sontheimer H . Cytoplasmic condensation is both necessary and sufficient to induce apoptotic cell death. J Cell Sci. 2008; 121(Pt 3):290-7. PMC: 2561226. DOI: 10.1242/jcs.017343. View

Ward I, Difilippantonio S, Minn K, Mueller M, Molina J, Yu X . 53BP1 cooperates with p53 and functions as a haploinsufficient tumor suppressor in mice. Mol Cell Biol. 2005; 25(22):10079-86. PMC: 1280262. DOI: 10.1128/MCB.25.22.10079-10086.2005. View

Puissant A, Fenouille N, Auberger P . When autophagy meets cancer through p62/SQSTM1. Am J Cancer Res. 2012; 2(4):397-413. PMC: 3410580. View

Zablotska L, Ron E, Rozhko A, Hatch M, Polyanskaya O, Brenner A . Thyroid cancer risk in Belarus among children and adolescents exposed to radioiodine after the Chornobyl accident. Br J Cancer. 2010; 104(1):181-7. PMC: 3039791. DOI: 10.1038/sj.bjc.6605967. View

10.

Matsuu-Matsuyama M, Shichijo K, Tsuchiya T, Kondo H, Miura S, Matsuda K . Protective effects of a cystine and theanine mixture against acute radiation injury in rats. Environ Toxicol Pharmacol. 2020; 78:103395. DOI: 10.1016/j.etap.2020.103395. View

11.

Matsuu-Matsuyama M, Nakashima M, Shichijo K, Okaichi K, Nakayama T, Sekine I . Basic fibroblast growth factor suppresses radiation-induced apoptosis and TP53 pathway in rat small intestine. Radiat Res. 2010; 174(1):52-61. DOI: 10.1667/RR1802.1. View

12.

Rodier F, Munoz D, Teachenor R, Chu V, Le O, Bhaumik D . DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion. J Cell Sci. 2010; 124(Pt 1):68-81. PMC: 3001408. DOI: 10.1242/jcs.071340. View

13.

Kurashige T, Nakajima Y, Shimamura M, Matsuyama M, Yamada M, Nakashima M . Basal Autophagy Deficiency Causes Thyroid Follicular Epithelial Cell Death in Mice. Endocrinology. 2019; 160(9):2085-2092. DOI: 10.1210/en.2019-00312. View

14.

Lee J, Yi S, Kang Y, Kim H, Joung K, Sul H . Morphological and Functional Changes in the Thyroid Follicles of the Aged Murine and Humans. J Pathol Transl Med. 2016; 50(6):426-435. PMC: 5122729. DOI: 10.4132/jptm.2016.07.19. View

15.

Veiga L, Holmberg E, Anderson H, Pottern L, Sadetzki S, Adams M . Thyroid Cancer after Childhood Exposure to External Radiation: An Updated Pooled Analysis of 12 Studies. Radiat Res. 2016; 185(5):473-84. PMC: 4893786. DOI: 10.1667/RR14213.1. View

16.

Kurohama H, Matsuda K, Kishino M, Yoshino M, Yamaguchi Y, Matsuu-Matsuyama M . Comprehensive analysis for detecting radiation-specific molecules expressed during radiation-induced rat thyroid carcinogenesis. J Radiat Res. 2021; 62(Supplement_1):i78-i87. PMC: 8114207. DOI: 10.1093/jrr/rraa139. View

17.

Chistiakov D, Voronova N, Chistiakov P . Genetic variations in DNA repair genes, radiosensitivity to cancer and susceptibility to acute tissue reactions in radiotherapy-treated cancer patients. Acta Oncol. 2008; 47(5):809-24. DOI: 10.1080/02841860801885969. View

18.

Al Rashid S, Harding S, Law C, Coackley C, Bristow R . Protein-protein interactions occur between p53 phosphoforms and ATM and 53BP1 at sites of exogenous DNA damage. Radiat Res. 2011; 175(5):588-98. DOI: 10.1667/RR2084.1. View

19.

Lin C, Whang E, Abramson M, Jiang X, Price B, Donner D . Autophagy: a new target for advanced papillary thyroid cancer therapy. Surgery. 2009; 146(6):1208-14. DOI: 10.1016/j.surg.2009.09.019. View

20.

Aratani S, Tagawa M, Nagasaka S, Sakai Y, Shimizu A, Tsuruoka S . Radiation-induced premature cellular senescence involved in glomerular diseases in rats. Sci Rep. 2018; 8(1):16812. PMC: 6235850. DOI: 10.1038/s41598-018-34893-8. View