Carcinogenesis Advance Access published online on February 3, 2005
Carcinogenesis, doi:10.1093/carcin/bgi039
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Surgery, Medical College of Ohio, Toledo, Ohio
* To whom correspondence should be addressed. Human ovarian cancer is predominantly of epithelial cell origin (>90% of malignant tumors) and most often presents at advanced stage with poor prognosis. Most animal models of ovarian carcinoma yield thecal/granulosa cell tumors, rather than adenocarcinomas. Induction of adenocarcinoma in 10-45% of rats following ovarian implantation of DMBA coated silk suture has been reported. Here DMBA of 99% purity was melted at 124°C to impregnate a 1 cm length of sterile suture for direct ovarian implantation in Wistar Furth rats at 7 wk of age. DMBA treated ovaries showed nearly complete loss of primary follicles and degeneration of granulosa cells at 16 wk, consistent with known toxic response of the ovary to direct DMBA application. No tumors were present. Untreated right ovaries and sham dimethylsulfoxide treated ovaries were normal. Ovarian tumors in DMBA treated rats were first noted 26 wk post implantation reaching a cumulative tumor incidence of 77% (23/30) at 52 wk. Controls showed no evidence of tumor at 52 wks (0/31). Tumor histology was distributed as well differentiated adenocarcinoma (1/23), poorly differentiated adenocarcinoma (8/23), thecal/granulosa cell tumor (8/23), undifferentiated sarcoma (5/23) and 1 undifferentiated carcinoma with no adeno character. Tumors occasionally seeded to peritoneal mesentery, spleen and abdominal wall. Adenocarcinomas appeared to originate from the ovarian surface epithelium, with focal papillary extension into cystic space. Epithelial derived tumor cells positively react with antibodies to cytokeratin (8/8), epithelial cell adhesion molecule (Ep-CAM 5/5) and prostaglandin synthetase-1 (COX-1 4/4). Vimentin positive epithelial cells when present in adenocarcinomas (4/7), showed perinuclear staining, quite different from uniformly stained stromal cells in thecal/granulosa cell tumors (8/8). The thecal/granulosa cell tumors were Ep-CAM negative (0/5) and weakly COX-1 positive (4/4). Thus the DMBA suture model in rats yields epithelial derived tumors histologically similar to humans and should prove suitable for testing preventive or therapeutic agents.
Received July 15, 2004
Revised January 6, 2005
Accepted January 28, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Characterization of rat ovarian adenocarcinomas developed in response to direct instillation of 7,12-dimethylbenz[a]anthracene (DMBA) coated suture
2 Department of Surgery and The Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Mo
3 Department of Pathology, Medical College of Ohio, Toledo, Ohio
4 Chemoprevention Agent Development Group, National Cancer Institute, Rockville, Maryland
Keith A. Crist, E-mail: kcrist{at}mco.edu
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. A. Hakim, C. P. Barry, H. J. Barnes, K. E. Anderson, J. Petitte, R. Whitaker, J. M. Lancaster, R. M. Wenham, D. K. Carver, J. Turbov, et al. Ovarian Adenocarcinomas in the Laying Hen and Women Share Similar Alterations in p53, ras, and HER-2/neu Cancer Prevention Research, February 1, 2009; 2(2): 114 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Y. Ting, B. F. Kimler, C. J. Fabian, and B. K. Petroff Tamoxifen Prevents Premalignant Changes of Breast, but not Ovarian, Cancer in Rats at High Risk for Both Diseases Cancer Prevention Research, December 1, 2008; 1(7): 546 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. Murdoch, E. A. Van Kirk, and Youqing Shen Pathogenic Reactions of the Ovarian Surface Epithelium to Ovulation, Dimethylbenzanthracene, and Estrogen are Negated by Vitamin E Reproductive Sciences, October 1, 2008; 15(8): 839 - 845. [Abstract] [PDF]
|
|
|
|
 |
|
 Y. Wang, Z. Zhang, Y. Lu, R. Yao, D. Jia, W. Wen, M. LaRegina, K. Crist, R. Lubet, and M. You Enhanced Susceptibility to Chemical Induction of Ovarian Tumors in Mice with a Germ Line p53 Mutation Mol. Cancer Res., January 1, 2008; 6(1): 99 - 109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Y. Ting, B. F. Kimler, C. J. Fabian, and B. K. Petroff Characterization of a preclinical model of simultaneous breast and ovarian cancer progression Carcinogenesis, January 1, 2007; 28(1): 130 - 135. [Abstract] [Full Text] [PDF]
|
|