Background: H2O2 produced in large quantities in the thyroid may play a role in the pathogenesis of thyroid nodules and cancer. In vitro, moderate amounts of H2O2 are able to cause similar DNA damage compared to irradiation and even to induce RET/PTC rearrangements.
Objective and hypotheses: We compared the defence mechanisms against H2O2 and irradiation in human thyrocytes, T-cells and other cell types.
Method: Human thyrocytes in primary culture were compared to other cell types: human T-cells in primary culture, a human thyroid epithelial cell line (Nthy-ori 3-1), non-transformed rat fibroblasts (F208) and a human myeloid cell line (PLB-XGCD) in terms of ability to degrade H2O2, glutathione peroxidase (GPx) activity, heme oxygenase-1 (HO-1) expression, cell survival and capacity to repair DNA damage after H2O2 exposure or irradiation.
Results: Thyrocytes rapidly degraded extracellular H2O2. Addition of BSO increased DNA damages in thyrocytes but not in T-cells. In the presence of H2O2, only the thyrocyte was able to increase GPx activity. Four to eight hours after treatment with H2O2, HO-1 expression was up-regulated in the thyrocyte. No significant regulation in HO-1 expression or GPx activity was observed after irradiation in all tested cell types. Finally, kinetics of repair performed after treatment with H2O2 or irradiation demonstrated that damages caused by irradiation are repaired more rapidly than those caused by H2O2 in all investigated cell types. T-cells were totally unable to repair damages caused by H2O2.
Conclusion: Thyrocyte have developed multiple mechanisms of protection against oxidative stress induced by H2O2. Our results suggest that deficiency of one of these mechanisms could promote the appearance of sporadic thyroid cancer. Due to their extreme sensitivity to H2O2, T-cells are probably not a good surrogate tissue to study individual susceptibility to H2O2.
Funding: This work was supported by the « Fonds Erasme pour la Recherche Médicale », The Belgian Kids Fund, FRS-FNRS, the Association Vinçotte Nuclear and the « Actions de Recherches Concertées de la Communauté Française de Belgique », the « Fonds Docteur J.P Naets » and Fondation Rose et Jean Hoguet.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology