Hydrogen peroxide induces DNA single- and double-strand breaks in thyroid cells and is therefore a potential mutagen for this organ.
DNA double-strand breaks (DSBs) are considered as one of the primary causes of cancer but their induction by hydrogen peroxide (H(2)O(2)) is still controversial. In this work, we studied whether the high levels of H(2)O(2) produced in the thyroid to oxidize iodide could induce DNA modifications. Scores of DNA damage, in terms of strand breaks, were obtained by comet assay (alkaline condition for single-strand breaks (SSBs) and neutral condition for DSBs). We demonstrated that in a rat thyroid cell line (PCCl3), non-lethal concentrations of H(2)O(2) (0.1-0.5 mmol/l) as well as irradiation (1-10 Gy) provoked a large number of SSBs ( approximately 2-3 times control DNA damage values) but also high levels of DSBs (1.2-2.3 times control DNA damage values). We confirmed the generation of DSBs in this cell line and also in human thyroid in primary culture and in pig thyroid slices by measuring phosphorylation of histone H2AX. L-Buthionine-sulfoximine, an agent that depletes cells of glutathione, decreased the threshold to observe H(2)O(2)-induced DNA damage. Moreover, we showed that DNA breaks induced by H(2)O(2) were more slowly repaired than those induced by irradiation. In conclusion, H(2)O(2) causes SSBs and DSBs in thyroid cells. DSBs are produced in amounts comparable with those observed after irradiation but with a slower repair. These data support the hypothesis that the generation of H(2)O(2) in thyroid could also play a role in mutagenesis particularly in the case of antioxidant defense deficiency.
Driessens
Natacha
N
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Faculty of Medicine, Université Libre de Bruxelles, Bat C Local C4.145, Campus Erasme, 808, Route de Lennik, B-1070 Brussels, Belgium. nadriess@ulb.ac.be
Versteyhe
Soetkin
S
Ghaddhab
Chiraz
C
Burniat
Agnès
A
De Deken
Xavier
X
Van Sande
Jacqueline
J
Dumont
Jacques-Emile
JE
Miot
Françoise
F
Corvilain
Bernard
B
D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D020552:Comet Assay; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D053904:DNA Breaks, Single-Stranded / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D013552:Swine; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects
D009153:Mutagens; D006861:Hydrogen Peroxide; D005978:Glutathione