Increased oxidative stress has been linked to thyroid carcinogenesis. In this 
paper, we investigate whether oxidative DNA damage and DNA repair differ in 
follicular adenoma (FA) and follicular thyroid carcinoma (FTC). 
7,8-Dihydro-8-oxoguanine (8-OxoG) formation was analysed by immunohistochemistry 
in 46 FAs, 52 FTCs and 18 normal thyroid tissues (NTs). mRNA expression of DNA 
repair genes OGG1, Mut Y homologue (MUTYH) and endonuclease III (NTHL1) was 
analysed by real-time PCR in 19 FAs, 25 FTCs and 19 NTs. Induction and repair of 
oxidative DNA damage were studied in rat FRTL-5 cells after u.v. irradiation. 
Moreover, activation of DNA damage checkpoints (ataxia telangiectasia mutated 
(ATM) and H2A histone family, member X (H2AFX (H2AFX))) and proliferation index 
(MIB-1) were quantified in 28 non-oxyphilic and 24 oxyphilic FTCs. Increased 
nuclear and cytosolic 8-OxoG formation was detected in FTC compared with 
follicular adenoma, whereby cytosolic 8-OxoG formation was found to reflect RNA 
oxidation. Significant downregulation of DNA repair enzymes was detected in FTC 
compared with FA. In vitro experiments mirrored the findings in FTC with 
oxidative stress-induced DNA checkpoint activation and downregulation of OGG1, 
MUTYH and NTHL1 in FRTL-5 cells, an effect that, however, was reversible after 
24  h. Further analysis of FTC variants showed decreased oxidative DNA damage, 
sustained checkpoint activation and decreased proliferation in oxyphilic vs 
non-oxyphilic FTC. Our data suggest a pathophysiological scenario of 
accumulating unrepaired DNA/RNA damage in FTC vs counterbalanced DNA/RNA damage 
and repair in FA. Furthermore, this study provides the first evidence for 
differences in oxidative stress defence in FTC variants with possible 
implications for therapeutic response and prognostic outcome.