Dissecting the Role of Thyrotropin in the DNA Damage Response in Human Thyrocytes after 131I, γ Radiation and H2O2.
J Clin Endocrinol Metab
; 105(3)2020 03 01.
Article
en En
| MEDLINE
| ID: mdl-31701151
ABSTRACT
BACKGROUND:
The early molecular events in human thyrocytes after 131I exposure have not yet been unravelled. Therefore, we investigated the role of TSH in the 131I-induced DNA damage response and gene expression in primary cultured human thyrocytes.METHODS:
Following exposure of thyrocytes, in the presence or absence of TSH, to 131I (ß radiation), γ radiation (3 Gy), and hydrogen peroxide (H2O2), we assessed DNA damage, proliferation, and cell-cycle status. We conducted RNA sequencing to profile gene expression after each type of exposure and evaluated the influence of TSH on each transcriptomic response.RESULTS:
Overall, the thyrocyte responses following exposure to ß or γ radiation and to H2O2 were similar. However, TSH increased 131I-induced DNA damage, an effect partially diminished after iodide uptake inhibition. Specifically, TSH increased the number of DNA double-strand breaks in nonexposed thyrocytes and thus predisposed them to greater damage following 131I exposure. This effect most likely occurred via Gαâq cascade and a rise in intracellular reactive oxygen species (ROS) levels. ß and γ radiation prolonged thyroid cell-cycle arrest to a similar extent without sign of apoptosis. The gene expression profiles of thyrocytes exposed to ß/γ radiation or H2O2 were overlapping. Modulations in genes involved in inflammatory response, apoptosis, and proliferation were observed. TSH increased the number and intensity of modulation of differentially expressed genes after 131I exposure.CONCLUSIONS:
TSH specifically increased 131I-induced DNA damage probably via a rise in ROS levels and produced a more prominent transcriptomic response after exposure to 131I.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Tirotropina
/
Rayos gamma
/
Peróxido de Hidrógeno
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Radioisótopos de Yodo
Límite:
Humans
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2020
Tipo del documento:
Article
País de afiliación:
Bélgica