Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure

PLoS One. 2020 Dec 31;15(12):e0244098. doi: 10.1371/journal.pone.0244098. eCollection 2020.

Abstract

Background: 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. 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 methods: Male 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.

Results: Nine 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.

Conclusion: Exposure-related and dose-related effects on gene and protein expression generated few expression patterns useful as biomarkers for thyroid function and cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Proteins / metabolism*
  • Calcium Signaling* / drug effects
  • Calcium Signaling* / radiation effects
  • Iodine Radioisotopes / pharmacology*
  • Male
  • Proteome / metabolism*
  • Proteomics
  • Rats
  • Rats, Sprague-Dawley
  • Thyroid Gland / metabolism*
  • Transcriptome* / drug effects
  • Transcriptome* / radiation effects

Substances

  • Blood Proteins
  • Iodine Radioisotopes
  • Iodine-131
  • Proteome

Grants and funding

EFA BioCARE – a National Strategic Research Program at the University of Gothenburg (https://www.lucc.lu.se/innovation-collaboration/collaboration/biocare-2010-2019), the Swedish Cancer Society (grant no. 3427), the Swedish Research Council (grant no. 21073 URL https://www.vr.se/), the Swedish state under the agreement between the Swedish government and the county councils – the ALF-agreement (ALFGBG-725031 URL https://www.vr.se/english/mandates/clinical-research/clinical-research-within-the-alf-agreement.html), Swedish Radiation Safety Authority (SSM URLhttps://www.stralsakerhetsmyndigheten.se/en/), the King Gustav V Jubilee Clinic Cancer Research Foundation (URLhttps://www.rahfo.se/om-oss/konung-gustaf-vs-jubileumsfond/), ML/NR the Sahlgrenska University Hospital Research Funds (URL https://www.vgregion.se/om-vgr/stiftelser-gavor-och-bidrag/), the Assar Gabrielsson Cancer Research Foundation (URL http://www.agfond.se/4.78c1e4631455d30294512c05.html).