This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stewart, S. L. Articles by Patriotis, C. Search for Related Content PubMed PubMed Citation Articles by Stewart, S. L. Articles by Patriotis, C.

Characterization of a Carcinogenesis Rat Model of Ovarian Preneoplasia and Neoplasia

¹ Medical Science Division and ² Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania

Animal models of ovarian cancer are crucial for understanding the pathogenesis of the disease and for testing new treatment strategies. A model of ovarian carcinogenesis in the rat was modified and improved to yield ovarian preneoplastic and neoplastic lesions that pathogenetically resemble human ovarian cancer. A significantly lower dose (2 to 5 µg per ovary) of 7,12-dimethylbenz(a)anthracene (DMBA) was applied to the one ovary to maximally preserve its structural integrity. DMBA-induced mutagenesis was additionally combined with repetitive gonadotropin hormone stimulation to induce multiple cycles of active proliferation of the ovarian surface epithelium. Animals were treated in three arms of different doses of DMBA alone or followed by hormone administration. Comparison of the DMBA-treated ovaries with the contralateral control organs revealed the presence of epithelial cell origin lesions at morphologically distinct stages of preneoplasia and neoplasia. Their histopathology and path of dissemination to other organs are very similar to human ovarian cancer. Hormone cotreatment led to an increased lesion severity, indicating that gonadotropins may promote ovarian cancer progression. Point mutations in the Tp53 and Ki-Ras genes were detected that are also characteristic of human ovarian carcinomas. Additionally, an overexpression of estrogen and progesterone receptors was observed in preneoplastic and early neoplastic lesions, suggesting a role of these receptors in ovarian cancer development. These data indicate that this DMBA animal model gives rise to ovarian lesions that closely resemble human ovarian cancer and it is adequate for additional studies on the mechanisms of the disease and its clinical management.

This article has been cited by other articles:

				J.-H. Choi, A. S. T. Wong, H.-F. Huang, and P. C. K. Leung Gonadotropins and Ovarian Cancer Endocr. Rev., June 1, 2007; 28(4): 440 - 461. [Abstract] [Full Text] [PDF]

				G. S. Gotfredson and W. J. Murdoch A BRIEF COMMUNICATION: Morphologic Responses of the Mouse Ovarian Surface Epithelium to Ovulation and Steroid Hormonal Milieu Experimental Biology and Medicine, February 1, 2007; 232(2): 277 - 280. [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]

				W. J. Murdoch Carcinogenic Potential of Ovulatory Genotoxicity Biol Reprod, October 1, 2005; 73(4): 586 - 590. [Abstract] [Full Text] [PDF]

				K. A. Crist, Z. Zhang, M. You, W. T. Gunning, P. B. Conran, V. E. Steele, and R. A. Lubet Characterization of rat ovarian adenocarcinomas developed in response to direct instillation of 7,12-dimethylbenz[a]anthracene (DMBA) coated suture Carcinogenesis, May 1, 2005; 26(5): 951 - 957. [Abstract] [Full Text] [PDF]