title: Ovarian neoplasm development by 7,12-dimethylbenz[a]anthracene (DMBA) in a chemically-induced rat model of ovarian failure.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Physiology, the University of Arizona, College of Medicine, 1501 N. Campbell Avenue, Tucson, AZ 85724-5051, USA. hoyer@u.arizona.edu
authors.forename: P B
authors.initials: PB
authors.lastname: Hoyer
authors.forename: J R
authors.initials: JR
authors.lastname: Davis
authors.forename: J B
authors.initials: JB
authors.lastname: Bedrnicek
authors.forename: S L
authors.initials: SL
authors.lastname: Marion
authors.forename: P J
authors.initials: PJ
authors.lastname: Christian
authors.forename: J K
authors.initials: JK
authors.lastname: Barton
authors.forename: M A
authors.initials: MA
authors.lastname: Brewer
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage*; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage*; D053138:Cyclohexenes / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D006080:Ovarian Follicle / Q000187:drug effects / Q000473:pathology; D010051:Ovarian Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D014753:Vinyl Compounds / Q000008:administration & dosage*
chemical_list: D002273:Carcinogens; D053138:Cyclohexenes; D014753:Vinyl Compounds; D015127:9,10-Dimethyl-1,2-benzanthracene; C012606:4-vinyl-1-cyclohexene dioxide