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

Ken Yamaguchi, Masaki Mandai, Mandai M, Toyokuni S, Shinya Toyokuni, Junzo Hamanishi, Toshihiro Higuchi, Higuchi T, Kenji Takakura, Takakura K, Fujii S, Shingo Fujii
Clinical cancer research : an official journal of the American Association for Cancer Research · 2008 · vol. 14(1) , pp. 32–40 · doi:10.1158/1078-0432.ccr-07-1614 · PMID:18172249 · W2127488625
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Endometriotic cysts contain high concentrations of free iron, leading to oxidative stress and DNA mutations, which may contribute to their malignant transformation.

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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.

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Condition tags

endometriosis

MeSH descriptors

Cyst Fluid Endometriosis Iron Ovarian Cysts Oxidative Stress Precancerous Conditions 8-Hydroxy-2'-Deoxyguanosine 8-Hydroxy-2'-Deoxyguanosine Cell Transformation, Neoplastic Cell Transformation, Neoplastic Cyst Fluid Cyst Fluid Cyst Fluid Deoxyguanosine Deoxyguanosine Deoxyguanosine Deoxyguanosine DNA Damage DNA Damage DNA Damage

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