title: 4-Vinylcyclohexene diepoxide (VCD) inhibits mammary epithelial differentiation and induces fibroadenoma formation in female Sprague Dawley rats.
abstract: 4-Vinylcyclohexene diepoxide (VCD), an occupational chemical that targets ovarian follicles and accelerates ovarian failure in rodents, was used to test the effect of early-onset reproductive senescence on mammary fibroadenoma formation. One-month female Sprague Dawley rats were dosed with VCD (80 mg/kg or 160 mg/kg) and monitored for 22 months for persistent estrus and tumor development. Only high-dose VCD treatment accelerated the onset of persistent estrus relative to controls. However, both doses of VCD accelerated mammary tumor onset by 5 months, increasing incidence to 84% (vs. 38% in controls). Tumor development was independent of time in persistent estrus, 17 β-estradiol, androstenedione and prolactin. Delay in VCD administration until after completion of mammary epithelial differentiation (3 months) did not alter tumor formation despite acceleration of ovarian senescence. VCD administration to 1-month rats acutely decreased mammary alveolar bud number and expression of β-casein, suggesting that VCD's tumorigenic effect requires exposure during mammary epithelial differentiation.
authors.affiliation: Department of Medicine, The University of Arizona, 1656 E Mabel St., PO Box 245218, Tucson, AZ 85724, United States. Lauraw1@u.arizona.edu
authors.forename: Laura E
authors.initials: LE
authors.lastname: Wright
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Frye
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Lukefahr
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Marion
authors.forename: Patricia B
authors.initials: PB
authors.lastname: Hoyer
authors.forename: David G
authors.initials: DG
authors.lastname: Besselsen
authors.forename: Janet L
authors.initials: JL
authors.lastname: Funk
mesh_terms: D000818:Animals; D002364:Caseins / Q000235:genetics / Q000378:metabolism; D053138:Cyclohexenes / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D018226:Fibroadenoma / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011388:Prolactin / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014753:Vinyl Compounds / Q000633:toxicity*
chemical_list: D002364:Caseins; D053138:Cyclohexenes; D004785:Environmental Pollutants; D014753:Vinyl Compounds; C012606:4-vinyl-1-cyclohexene dioxide; D011388:Prolactin; D019009:Proto-Oncogene Proteins c-kit