ESPE Abstracts

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 H₂O_2.

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.