Gene expression signature in mouse thyroid tissue after 131I and 211At exposure

• Background 131 I and 211 At are used in nuclear medicine and accumulate in the thyroid gland and may impact normal thyroid function. The aim of this study was to determine transcriptional profile variations, assess the impact on cellular activity, and identify genes with biomarker properties in thyroid tissue after 131 I and 211 At administration in mice. Methods To further investigate thyroid tissue transcriptional responses to 131 I and 211 At administration, we generated a new transcriptional dataset that includes re-evaluated raw intensity values from our previous 131 I and 211 At studies. Differential transcriptional profiles were identified by comparing treated and mock-treated samples using Nexus Expression 3.0 software. Further data analysis was performed using R/Bioconductor and IPA. Results A total of 1144 genes were regulated. Hierarchical clustering subdivided the groups into two clusters containing the lowest and highest absorbed dose levels, respectively, and revealed similar transcriptional regulation patterns for many kallikrein-related genes. Twenty-seven of the 1144 genes were recurrently regulated after 131 I and 211 At exposure and divided into six clusters. Several signalling pathways were affected, including calcium, integrin-linked kinase, and thyroid cancer signalling, and the peroxisomal proliferator-activated receptor network. Conclusions Substantial changes in transcriptional regulation were shown in 131 I and 211 At-treated samples, and 27 genes were identified as potential biomarkers for 131 I and 211 At exposure. Clustering revealed distinct differences between transcriptional profiles of both similar and different exposures, demonstrating the necessity for better understanding of radiation-induced effects on cellular activity. Additionally, ionizing radiation-induced changes in kallikrein gene expression and identified canonical pathways should be further assessed. Keywords: Radiation biology; Microarray; Radiation biomarkers; Radionuclide therapy; Transcriptomics; Radiogenomics

Ämnesord

NATURVETENSKAP  -- Biologi -- Bioinformatik och systembiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

Radiation biology; Microarray; Radiation biomarkers; Radionuclide therapy; Transcriptomics; Radiogenomics

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)