Abstract
BackgroundRadioiodide (131I) is commonly used to treat thyroid cancer and hyperthyroidis.131I released during nuclear accidents, have resulted in increased incidence of thyroid cancer in children. Therefore, a better understanding of underlying cellular mechanisms behind 131I exposure is of great clinical and radiation protection interest. The aim of this work was to study the long-term dose-related effects of 131I exposure in thyroid tissue and plasma in young rats and identify potential biomarkers.Materials and methodsMale Sprague Dawley rats (5-week-old) were i.v. injected with 0.5, 5.0, 50 or 500 kBq 131I (Dthyroid ca 1–1000 mGy), and killed after nine months at which time the thyroid and blood samples were collected. Gene expression microarray analysis (thyroid samples) and LC-MS/MS analysis (thyroid and plasma samples) were performed to assess differential gene and protein expression profiles in treated and corresponding untreated control samples. Bioinformatics analyses were performed using the DAVID functional annotation tool and Ingenuity Pathway Analysis (IPA). The gene expression microarray data and LC-MS/MS data were validated using qRT-PCR and ELISA, respectively.ResultsNine 131I exposure-related candidate biomarkers (transcripts: Afp and RT1-Bb, and proteins: ARF3, DLD, IKBKB, NONO, RAB6A, RPN2, and SLC25A5) were identified in thyroid tissue. Two dose-related protein candidate biomarkers were identified in thyroid (APRT and LDHA) and two in plasma (DSG4 and TGM3). Candidate biomarkers for thyroid function included the ACADL and SORBS2 (all activities), TPO and TG proteins (low activities). 131I exposure was shown to have a profound effect on metabolism, immune system, apoptosis and cell death. Furthermore, several signalling pathways essential for normal cellular function (actin cytoskeleton signalling, HGF signalling, NRF2-mediated oxidative stress, integrin signalling, calcium signalling) were also significantly regulated.ConclusionExposure-related and dose-related effects on gene and protein expression generated few expression patterns useful as biomarkers for thyroid function and cancer.
Highlights
The thyroid is an endocrine gland that produces iodine-containing hormones involved in metabolism and brain development
Candidate biomarkers for thyroid function included the ACADL and SORBS2, thyroid peroxidase (TPO) and TG proteins. 131I exposure was shown to have a profound effect on metabolism, immune system, apoptosis and cell death
The proteomic analysis identified 792 and 273 differentially expressed proteins associated with 131I exposure in thyroid tissue (Fig 1B) and plasma (Fig 1C), respectively
Summary
The thyroid is an endocrine gland that produces iodine-containing hormones involved in metabolism and brain development. According to the Swedish Radiation Safety Authority (2019), the absorbed dose to thyroid in adults was 0.063– 7.2 Gy for diagnostics, and 60–2600 Gy for therapy [2, 3]. 131I-MIBG therapy resulted in around 2 Gy absorbed dose to thyroid in young children. For medical use 131I is usually produced by (n, γ) reaction of 130Te to 131Te (half-life 25 min), which decays to 131I. Another way is by separation of fission products from 235U [4]. Radioiodide (131I) is commonly used to treat thyroid cancer and hyperthyroidis.131I released during nuclear accidents, have resulted in increased incidence of thyroid cancer in children. The aim of this work was to study the long-term dose-related effects of 131I exposure in thyroid tissue and plasma in young rats and identify potential biomarkers.
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