Free Iron In Endometriotic Carcinoma
ironjustice
Fujii S
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 Article]
Clin Cancer Res 2008 Jan 1; 14(1):32-40.
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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Clinical cancer research : an official journal of the American
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