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

Sci Rep. 2021 Sep 27;11(1):19096. doi: 10.1038/s41598-021-98481-z.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Animals
  • Carcinogenesis / radiation effects*
  • Child
  • Dose-Response Relationship, Radiation
  • Humans
  • Incidence
  • Male
  • Neoplasms, Radiation-Induced / epidemiology*
  • Neoplasms, Radiation-Induced / etiology
  • Neoplasms, Radiation-Induced / pathology
  • Radiation Injuries, Experimental / epidemiology*
  • Radiation Injuries, Experimental / etiology
  • Radiation Injuries, Experimental / pathology
  • Radiation Tolerance
  • Rats
  • Risk Factors
  • Thyroid Gland / pathology
  • Thyroid Neoplasms / epidemiology*
  • Thyroid Neoplasms / etiology
  • Thyroid Neoplasms / pathology
  • X-Rays / adverse effects