RRC ID 6782
Author Yamaguchi K, Mandai M, Toyokuni S, Hamanishi J, Higuchi T, Takakura K, Fujii S.
Title Contents of endometriotic cysts, especially the high concentration of free iron, are a possible cause of carcinogenesis in the cysts through the iron-induced persistent oxidative stress.
Journal Clin. Cancer Res.
Abstract PURPOSE:Endometriotic cysts are known to transform into ovarian cancers, such as clear cell and endometrioid carcinomas. We hypothesized that an iron-rich environment produced by the repetition of hemorrhage in the endometriotic cysts during the reproductive period may play a crucial role in carcinogenesis in the cysts through the iron-induced persistent oxidative stress.
EXPERIMENTAL DESIGN:Contents of human ovarian cysts, including 21 endometriotic cysts, 4 clear cell carcinomas, and 11 nonendometriotic cysts, were analyzed for the concentrations of free "catalytic" iron, lactose dehydrogenase, potential antioxidant, lipid peroxide, and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Iron deposition and 8-OHdG levels were also analyzed histologically. Reactive oxygen species and the mutagenicity of the contents in endometriotic cyst were determined in vitro.
RESULTS:The concentration of free iron in endometriotic cysts (100.9 mmol/L) was significantly higher than that in nonendometriotic cysts (0.075 mmol/L; P < 0.01). The average concentrations of lactose dehydrogenase, potential antioxidant, lipid peroxide, and 8-OHdG were also significantly higher in endometriotic cysts (P < 0.01). There was a correlation between the concentration of free iron and that of 8-OHdG (P < 0.01). Histologically, we could observe iron deposits more abundantly in endometriotic cysts than in nonendometriotic cysts (P < 0.01). The level of 8-OHdG in carcinoma associated with endometriosis was higher than that of carcinoma without endometriosis (P < 0.05). In vitro analyses showed that the contents of endometriotic cyst could produce more reactive oxygen species and could induce gene mutations more frequently than the contents in the other cysts.
CONCLUSIONS:Abundant free iron in the contents of endometriotic cysts was strongly associated with greater oxidative stress and frequent DNA mutations. A long-standing history of the RBCs accumulated in the ovarian endometriotic cysts during the reproductive period produces oxidative stress that is a possible cause for the malignant change of the endometriotic cyst.
Volume 14(1)
Pages 32-40
Published 2008-1-1
DOI 10.1158/1078-0432.CCR-07-1614
PII 14/1/32
PMID 18172249
MeSH Cell Transformation, Neoplastic Cyst Fluid / chemistry* Cyst Fluid / metabolism DNA Damage / drug effects Deoxyguanosine / analogs & derivatives Deoxyguanosine / analysis Endometrial Neoplasms / pathology Endometriosis / pathology* Female Humans Immunohistochemistry Iron / adverse effects Iron / analysis* L-Lactate Dehydrogenase / analysis Ovarian Cysts / chemistry Ovarian Cysts / pathology* Oxidative Stress / physiology* Precancerous Conditions / pathology* Reactive Oxygen Species
IF 8.911
Times Cited 122
Human and Animal Cells