Ovarian neoplasm development by 7,12-dimethylbenz[a]anthracene (DMBA) in a chemically-induced rat model of ovarian failure

Patricia B Hoyer, J. R. Davis, J. B. Bedrnicek, S. L. Marion, P. J. Christian, Jennifer K Barton, M. A. Brewer

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Objectives: The objectives were to determine the time course for ovarian failure in rats caused by 4-vinylcyclohexene diepoxide (VCD) and develop a model for ovarian cancer in which ovarian neoplasms were chemically induced in an animal that was follicle depleted, but retained residual ovarian tissue. Methods: Initially, female Fisher 344 rats were treated with VCD (to induce ovarian failure) or vehicle control (sesame oil). Three or 6 months after treatment, ovaries were collected and processed for histological evaluation for confirmation of ovarian failure. A further set of female rats was assigned to four groups exposed to combinations of vehicle control, VCD and/or DMBA (directly applied to the ovary) in a novel model for examining early stages of ovarian neoplasia. Results: Three and 6 months following VCD dosing there was a significant reduction of ovarian weight and follicle number. Treatment with DMBA subsequent to VCD resulted in tumors in 42% of animals at 3 months and 57% at 5 months. All neoplasms were classified Sertoli-Leydig cell tumors (SLCT). No tumor occurred in animals treated with vehicle or DMBA alone. Conclusions: These studies demonstrate that the VCD-treated rat can be used as a model for peri- and post-menopause. DMBA induction of ovarian neoplasms was greater in those rats treated with VCD. Whether this increase was due to tumor initiation by VCD or was the result of ovarian failure cannot be distinguished from these results. This represents the only animal model to date for sex cord stromal tumors.

Original languageEnglish (US)
Pages (from-to)610-615
Number of pages6
JournalGynecologic Oncology
Volume112
Issue number3
DOIs
StatePublished - Mar 2009

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9,10-Dimethyl-1,2-benzanthracene
Ovarian Neoplasms
Neoplasms
Ovary
Sex Cord-Gonadal Stromal Tumors
Sertoli-Leydig Cell Tumor
Sesame Oil
Postmenopause
Ovarian Follicle
anthracene
4-vinyl-1-cyclohexene dioxide
Menopause
Weight Loss
Animal Models

Keywords

  • 4-vinylcyclohexene diepoxide
  • 7,12-dimethylbenz[a]anthracene
  • Ovarian failure
  • Ovarian neoplasm
  • Rat model

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Ovarian neoplasm development by 7,12-dimethylbenz[a]anthracene (DMBA) in a chemically-induced rat model of ovarian failure. / Hoyer, Patricia B; Davis, J. R.; Bedrnicek, J. B.; Marion, S. L.; Christian, P. J.; Barton, Jennifer K; Brewer, M. A.

In: Gynecologic Oncology, Vol. 112, No. 3, 03.2009, p. 610-615.

Research output: Contribution to journalArticle

Hoyer, Patricia B ; Davis, J. R. ; Bedrnicek, J. B. ; Marion, S. L. ; Christian, P. J. ; Barton, Jennifer K ; Brewer, M. A. / Ovarian neoplasm development by 7,12-dimethylbenz[a]anthracene (DMBA) in a chemically-induced rat model of ovarian failure. In: Gynecologic Oncology. 2009 ; Vol. 112, No. 3. pp. 610-615.
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abstract = "Objectives: The objectives were to determine the time course for ovarian failure in rats caused by 4-vinylcyclohexene diepoxide (VCD) and develop a model for ovarian cancer in which ovarian neoplasms were chemically induced in an animal that was follicle depleted, but retained residual ovarian tissue. Methods: Initially, female Fisher 344 rats were treated with VCD (to induce ovarian failure) or vehicle control (sesame oil). Three or 6 months after treatment, ovaries were collected and processed for histological evaluation for confirmation of ovarian failure. A further set of female rats was assigned to four groups exposed to combinations of vehicle control, VCD and/or DMBA (directly applied to the ovary) in a novel model for examining early stages of ovarian neoplasia. Results: Three and 6 months following VCD dosing there was a significant reduction of ovarian weight and follicle number. Treatment with DMBA subsequent to VCD resulted in tumors in 42{\%} of animals at 3 months and 57{\%} at 5 months. All neoplasms were classified Sertoli-Leydig cell tumors (SLCT). No tumor occurred in animals treated with vehicle or DMBA alone. Conclusions: These studies demonstrate that the VCD-treated rat can be used as a model for peri- and post-menopause. DMBA induction of ovarian neoplasms was greater in those rats treated with VCD. Whether this increase was due to tumor initiation by VCD or was the result of ovarian failure cannot be distinguished from these results. This represents the only animal model to date for sex cord stromal tumors.",
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AU - Marion, S. L.

AU - Christian, P. J.

AU - Barton, Jennifer K

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