Effect of low-dose internal radioactive iodine exposure on transcriptional activity of radiation-specific genes and cellular proliferation in rat thyroid

Abstract

OBJECTIVE The thyroid gland is a radiosensitive organ and concerns about low grade radiation exposure on thyroid gland is increasing. However, the comprehensive in-vivo data area is limited. In this study, we analyzed the functional, anatomical, and molecular genetic changes of thyroid gland in young and adult rat model after internal exposure to different dose of 131-Iodine.

RESEARCH DESIGN AND METHODS This study included female Sprague-Dawley rats aged 4 weeks and 12 weeks. The 131-Iodine doses were 5 uCi and 250 uCi and they were injected via tail vein of rats in treatment groups. After administration of 131-Iodine, the functional and morphologic changes were assessed by sacrificing animal in predetermined intervals. For subset of 4 weeks-aged rats, we performed microarray analysis to elucidate the acute and latent transcriptional responses to different dose of 131-Iodine and performed real-time quantitative PCR to validate the microarray expression data.

RESULTS In high dose exposed group, atrophy of thyroid gland and fibrosis were observed without functional deterioration. In low dose exposed group, there were no significant functional or morphologic changes in both young and adult rats. In network transcriptional analysis of young rats, various metabolic and CYP450 pathways were up-regulated transiently after 5 uCi exposure. In 20 weeks, immune pathways became predominant. The 5 uCi exposure lead to transient overexpression of p53 pathway and apoptosis related genes both in young and adult rats.

CONCLUSION The low dose exposure of 131-Iodine did not lead to significant morphologic or functional changes to thyroid gland, suggesting successful adaptation to radiation exposure by coordinated transcriptional response including p53 pathway genes. The effect of this distinct adaptive responses induced by low dose radiation on thyroid cancer risk remains to be determined.