Oxidative stress in the thyroid – DNA damage and repair: Important mechanisms in the pathogenesis of thyroid tumours?

Abstract

Oxidative stress due to an imbalance between pro-and antioxidative factors could be an important mechanism in the pathogenesis of thyroid diseases. We performed an IHC study to address the extent of 8-hydroxy-2'-deoxyguanine (8oxoG) formation, a key indicator of oxidative DNA base damage, in benign and malignant thyroid nodules. Besides we studied the enzyme expression of OGG-1, MYH and NTH responsible for repair of oxidative DNA damage. Ten toxic thyroid nodules (TTN), 14 cold benign thyroid nodules (CTN), their respective normal surrounding tissues (NT), 20 follicular (FTC), 18 papillary (PTC), 2 anaplastic (ATC), 5 medullary thyroid cancers (MTC) and 7 Graves' disease (GD) samples were investigated. Thyroid cancers showed a strong, morphology-specific subcellular 8oxoG staining pattern. In PTC, cytoplasmatic labelling was prevailing, suggesting vantaged mitochondrial DNA damage. In contrast, prominent nuclear staining was noticed in FTC. Comparison of differentially functioning benign thyroid nodules showed at least 2x increase in cytoplasmatic labelling in CTN compared to NT, while no difference was observed for TTN, their NT and GD. OGG-1, MYH and NTH mRNA expression was detected in all examined thyroid tissues with a significant downregulation of all 3 repair enzymes in FTC. In PTC we observed also a clear trend of downregulation but data failed to reach significance.