Iodine deficiency activates antioxidant genes and causes DNA damage in the thyroid gland of rats and mice.
Because thyroid nodules are frequent in areas with iodine deficiency the aim of this study was to characterise molecular events during iodine deficiency that could explain mutagenesis and nodule formation. We therefore studied gene expression of catalytic enzymes prominent for H(2)O(2) detoxification and antioxidative defence, quantified DNA oxidation and damage as well as spontaneous mutation rates (SMR) in mice and rats fed an iodine controlled diet. Antioxidative enzymes such as superoxide dismutase 3, glutathione peroxidase 4 and the peroxiredoxins 3 and 5 showed increased mRNA expression, which indicates increased radical burden that could be the cause of additional oxidized base adducts found in thyroidal genomic DNA in our experiments of iodine deficiency. Furthermore, the uracil content of thyroid DNA was significantly higher in the iodine-deficient compared to the control group. While SMR is very high in the normal thyroid gland it is not changed in experimental iodine deficiency. Our data suggest that iodine restriction causes oxidative stress and DNA modifications. A higher uracil content of the thyroid DNA could be a precondition for C-->T transitions often detected as somatic mutations in nodular thyroid tissue. However, the absence of increased SMR would argue for more efficient DNA repair in response to iodine restriction.
Maier
J
J
III Medical Department, Interdisciplinary Centre for Clinical Research, University of Leipzig, Leipzig, Germany.
van Steeg
H
H
van Oostrom
C
C
Paschke
R
R
Weiss
R E
RE
Krohn
K
K
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D015971:Gene Expression Regulation, Enzymologic; D006861:Hydrogen Peroxide / Q000378:metabolism; D007455:Iodine / Q000172:deficiency*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D016296:Mutagenesis; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D017354:Point Mutation; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000201:enzymology* / Q000473:pathology; D016606:Thyroid Nodule / Q000201:enzymology / Q000473:pathology; D014498:Uracil / Q000378:metabolism
D000975:Antioxidants; D014498:Uracil; D007455:Iodine; D006861:Hydrogen Peroxide; D010088:Oxidoreductases