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Distinct pattern of...
Distinct pattern of oxidative DNA damage and DNA repair in follicular thyroid tumours.
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- Karger, Stefan (author)
- Clinic of Endocrinology and Nephrology, Department of Internal Medicine, Neurology and Dermatology, University of Leipzig, Liebigstraße 18, 04103 Leipzig, Germany
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- Krause, Kerstin (author)
- Clinic of Endocrinology and Nephrology, Department of Internal Medicine, Neurology and Dermatology, University of Leipzig, Liebigstraße 18, 04103 Leipzig, Germany
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- Engelhardt, Cornelia (author)
- Clinic of Endocrinology and Nephrology, Department of Internal Medicine, Neurology and Dermatology, University of Leipzig, Liebigstraße 18, 04103 Leipzig, Germany
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- Weidinger, Carl (author)
- Clinic of Endocrinology and Nephrology, Department of Internal Medicine, Neurology and Dermatology, University of Leipzig, Liebigstraße 18, 04103 Leipzig, Germany
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- Gimm, Oliver (author)
- Department of General, Visceral, and Vascular Surgery, Martin Luther University of Halle‐Wittenberg, Ernst‐Grube‐Straße 40, 06120 Halle, Saale, Germany
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- Dralle, Henning (author)
- Department of General, Visceral, and Vascular Surgery, Martin Luther University of Halle‐Wittenberg, Ernst‐Grube‐Straße 40, 06120 Halle, Saale, Germany
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- Sheu-Grabellus, Sien-Yi (author)
- Institute of Pathology and Neuropathology, University of Duisburg-Essen, Essen, Germany
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- Kurt Werner, Schmid (author)
- Institute of Pathology and Neuropathology, University of Duisburg-Essen, Essen, Germany
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- Fuhrer, Dagmar (author)
- Clinic of Endocrinology and Metabolic Disorders, University of Duisburg‐Essen, Hufelandstraße 55, D-45147 Essen, Germany
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(creator_code:org_t)
- 2012
- 2012
- English.
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In: Journal of molecular endocrinology. - 1479-6813. ; 48:3, s. 193-202
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
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- art (subject category)
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