Endocrine Abstracts

Introduction: Radiation exposure at young ages is a risk of thyroid cancer. Although early studies of the infants treated with X-rays already indicated an association, the risk became well-known by a rapid rise in childhood thyroid cancer cases after the Chernobyl nuclear plant accident. Human cases have been investigated extensively, but the underlying mechanisms have yet to be elucidated. Our previous investigation in rats found that neonatal X-irradiation induced long-term mRNA expression changes in the thyroid cancer-related marker genes, which may be a key to understanding childhood susceptibility to thyroid carcinogenesis. Then, in the present study, we performed a global gene expression analysis to identify the thyroid genes whose expressions were altered by neonatal irradiation in the rat model.

Materials and Methods: Male Wistar rats at 1 week old (neonates) and 8 weeks old (adults) were cervically X-irradiated at 0, 6, or 12 Gy. After 8 weeks, the thyroid was dissected and subjected to the gene expression analysis by the RNA-Seq (20 million reads, 100 bp pair-end analysis) to classify the genes regulated by radiation. The expression changes in the newly identified genes were confirmed by Q-RT-PCR. The expression changes were further examined in the thyroid tumors induced by feeding with an iodine-deficient diet in rats.

Results: 1) The RNA-Seq analysis identified 114 up-regulated and 29 down-regulated thyroid genes in 8 weeks after irradiation. 2) A comparison between neonatal and adult irradiation found that 9 up-regulated and 5 down-regulated genes were specific to neonatal radiation exposure. 3) Among them, Cdkn1a and Vnn1 were identified as the up-regulated genes in the thyroid tumors.

Conclusions: We successfully identified a series of thyroid genes whose expression could be changed long-term after a single cervical irradiation during the neonatal period. Some of those genes, such as Cdkn1a and Vnn1, were also up-regulated in the thyroid tumors. These findings suggested that the alteration of gene expressions by neonatal radiation may contribute to the increased risk of thyroid cancer by childhood radiation exposure.