4-Vinylcyclohexene diepoxide (VCD) inhibits mammary epithelial differentiation and induces fibroadenoma formation in female Sprague Dawley rats

Laura E. Wright, Jennifer B. Frye, Ashley L. Lukefahr, Samuel L. Marion, Patricia B. Hoyer, David G. Besselsen, Janet L. Funk

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5 Scopus citations


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, 17β-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.

Original languageEnglish (US)
Pages (from-to)26-32
Number of pages7
JournalReproductive Toxicology
Issue number1
StatePublished - Jul 1 2011



  • C-KIT
  • Fibroadenoma
  • Mammary epithelium
  • VCD
  • β-Casein

ASJC Scopus subject areas

  • Toxicology

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