Dose-specific transcriptional responses in thyroid tissue in mice after 131I administration

Abstract

IntroductionIn the present investigation, microarray analysis was used to monitor transcriptional activity in thyroids in mice 24h after 131I exposure. The aims of this study were to 1) assess the transcriptional patterns associated with 131I exposure in normal mouse thyroid tissue and 2) propose biomarkers for 131I exposure of the thyroid. MethodsAdult BALB/c nude mice were i.v. injected with 13, 130 or 260kBq of 131I and killed 24h after injection (absorbed dose to thyroid: 0.85, 8.5, or 17Gy). Mock-treated mice were used as controls. Total RNA was extracted from thyroids and processed using the Illumina platform. ResultsIn total, 497, 546, and 90 transcripts were regulated (fold change ≥1.5) in the thyroid after 0.85, 8.5, and 17Gy, respectively. These were involved in several biological functions, e.g. oxygen access, inflammation and immune response, and apoptosis/anti-apoptosis. Approximately 50% of the involved transcripts at each absorbed dose level were dose-specific, and 18 transcripts were commonly detected at all absorbed dose levels. The Agpat9, Plau, Prf1, and S100a8 gene expression displayed a monotone decrease in regulation with absorbed dose, and further studies need to be performed to evaluate if they may be useful as dose-related biomarkers for 131I exposure. ConclusionDistinct and substantial differences in gene expression and affected biological functions were detected at the different absorbed dose levels. The transcriptional profiles were specific for the different absorbed dose levels. We propose that the Agpat9, Plau, Prf1, and S100a8 genes might be novel potential absorbed dose-related biomarkers to 131I exposure of thyroid. Advances in knowledgeDuring the recent years, genomic techniques have been developed; however, they have not been fully utilized in nuclear medicine and radiation biology. We have used RNA microarrays to investigate genome-wide transcriptional regulations in thyroid tissue in mice after low, intermediate, and high absorbed doses from 131I exposure in vivo. Using this approach, we have identified novel biological responses and potential absorbed dose-related biomarkers to 131I exposure. Our research shows the importance of embracing technological advances and multi-disciplinary collaboration in order to apply them in radiation therapy, nuclear medicine, and radiation biology. Implications on Patient CareThis work may contribute with new knowledge of potential normal tissue effects or complications that may occur after exposure to ionizing radiation in diagnostic and therapeutic nuclear medicine, and due to radioactive fallout or accident with radionuclide spread.