Astatine-211 exposure of Balb/c mice in vivo resulted in distinct effets on thyroid at 1, 6 hours and 7 days after injection

• Astatine-211 (211At) is a promising therapeutic radionuclide due to a nearly optimal linear energy transfer for generating double stand breaks in DNA. However, free 211At targets the thyroid gland due to chemical similarities with iodine. There are gaps in our knowledge about the general radiation-induced changes in basal cellular functions in thyroid tissue. The specific aim of this study was to investigate how global gene expression levels in thyroids change with time after 211At injection in mice. Female BALB/c nude mice were i.v. injected with 1.7 kBq 211At in the tail vein. The animals were killed at 1 hour, 6 hours, and 7 days post injection and the thyroids were removed and snap-frozen. The thyroids in each group were pooled and total RNA was extracted and processed using Illumina MouseRef-8 Whole-Genome Expression Beadchips. The gene expression in irradiated thyroids was compared with mock treated controls and regulated transcripts were associated with biological functions using Nexus Expression 2.0. Analysis revealed a distinct impact on global gene expression at all time points in thyroids exposed to 211At. The number of regulated transcripts decreased with time after injection (358, 260, and 193 at 1 h, 6 h, and 7 d, respectively). Generally, transcripts were more often down- than up-regulated. A total of 48 transcripts were detected at all time points (8 up- and 40 down-regulated). The regulated transcripts at the three separate times were associated with 66, 60, and 65 Gene Ontology terms (p < 0.05). At 1 and 6 h, DNA and gene expression integrity were affected and at 7 d after injection, an impact on cellular integrity was seen. A significant impact on transcripts involved in the immune system was also seen at all time points, but this was more pronounced at 1 h and 7 d. An inflammatory response was detected at 1 h but was even more distinct at 7 d. Conclusively, exposure to 211At caused a significant impact on normal cellular functions in thyroid tissue. Processes related to gene expression were affected early while at a later time point, radiation had an impact on processes related to cellular integrity. Interestingly, there was a decrease in the immune and inflammatory response at 6 h compared to either 1 hour or 7 d. Also, 48 transcripts were detected at all time points, which may be of interest for retrospective biodosimetry.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (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)

Publikations- och innehållstyp

vet (ämneskategori)

kon (ämneskategori)