Abstract：
OBJECTIVE:Ovarian carcinomas that originate from fallopian epithelial cells are suggested to arise due to repeated exposure to ovulatory follicular fluid (FF). Mechanistic explanation(s) for how this occurs are unknown. Here, we sought to understand if FF exposure to fallopian epithelial cells could induce DNA damage and expression of a known family of DNA mutators, apolipoprotein B mRNA editing enzyme, catalytic polypeptide (APOBEC) cytidine deaminases. METHODS:Follicular fluid and matched patient plasma samples were obtained from donors. Fallopian epithelial cells (FT33-TAg, FT189, FT190, and FT194) were cultured with FF or plasma for 24h, and cell proliferation and DNA damage were assessed. Effects of FF on Apobec gene expression were determined by qRT-PCR and western blot analyses. Fallopian epithelial cells were transfected with an APOBEC3A expression vector and DNA damage was assessed. RESULTS:Follicular fluid exposure increased epithelial cell proliferation as measured by three independent methods, and DNA damage accumulation as assessed using three independent measures. This effect was specific to FF, as matched patient plasma did not have the same effects. Increased expression of Apobec3a was observed in fallopian epithelial cells following exposure to 5 of 8 patient FF samples, and transient overexpression of APOBEC3A was sufficient to induce double strand DNA breaks. CONCLUSIONS:Follicular fluid can induce cell proliferation and DNA damage accumulation in cultured fallopian epithelial cells. Increased expression of APOBEC3A, a known DNA mutator, may explain the high incidence of DNA damage after FF exposure. The role of Apobec3a in ovulation-induced inflammation warrants further investigation.
journal_name
Gynecol Oncoljournal_title
Gynecologic oncologyauthors
Brachova P,Alvarez NS,Van Voorhis BJ,Christenson LKdoi
10.1016/j.ygyno.2017.02.017subject
Has Abstractpub_date
2017-06-01 00:00:00pages
577-583issue
3eissn
0090-8258issn
1095-6859pii
S0090-8258(17)30129-4journal_volume
145pub_type
杂志文章abstract：OBJECTIVE:To propose a risk-specific follow-up protocol for endometrial carcinoma patients. METHODS:A retrospective cohort of endometrial carcinoma patients was used to identify risk factors for recurrence. Based on a profile of risk factors, women were classified at either low or high risk for recurrence (median foll...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1006/gyno.1997.4698
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journal_title：Gynecologic oncology
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journal_title：Gynecologic oncology
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journal_title：Gynecologic oncology
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doi：10.1006/gyno.2001.6468
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abstract：:By serendipity we have had the opportunity to evaluate cis-platin-based chemotherapy in ovarian tumors of low malignant potential (LMP). Optimal (less than 1 cm residual disease) FIGO stage III ovarian carcinomas were randomly assigned to treatment with cisplatin plus cyclophosphamide with or without doxorubicin on a ...
journal_title：Gynecologic oncology
pub_type： 临床试验,杂志文章,随机对照试验
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abstract：OBJECTIVE:To identify novel prognostic and therapeutic markers for PARP inhibitors in BRCA wild type ovarian cancer (OvCa). METHODS:BRCAness status was defined by analyzing whole-exome deep sequencing data from 220 BRCAwt OvCa cases in TCGA. Thirty-three DNA-repair genes were screened in an integrated manner for BRCA-...
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pub_type： 临床试验,杂志文章,多中心研究
doi：10.1016/j.ygyno.2005.03.032
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pub_type： 临床试验,杂志文章
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pub_type： 杂志文章,评审
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更新日期：2012-12-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2019-05-01 00:00:00
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更新日期：2007-02-01 00:00:00
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pub_type： 杂志文章
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更新日期：1984-09-01 00:00:00
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pub_type： 杂志文章
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更新日期：1990-09-01 00:00:00
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pub_type： 杂志文章
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更新日期：2018-03-01 00:00:00
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更新日期：2008-12-01 00:00:00
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更新日期：1997-01-01 00:00:00
