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

Reprod Toxicol. 2011 Jul;32(1):26-32. doi: 10.1016/j.reprotox.2011.05.005. Epub 2011 May 20.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caseins / genetics
  • Caseins / metabolism
  • Cyclohexenes / toxicity*
  • Environmental Pollutants / toxicity*
  • Estrous Cycle / drug effects
  • Female
  • Fibroadenoma / chemically induced*
  • Fibroadenoma / metabolism
  • Fibroadenoma / pathology
  • Gene Expression Regulation, Developmental / drug effects
  • Mammary Glands, Animal / drug effects*
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Animal / pathology
  • Mammary Neoplasms, Animal / chemically induced*
  • Mammary Neoplasms, Animal / metabolism
  • Mammary Neoplasms, Animal / pathology
  • Prolactin / metabolism
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Vinyl Compounds / toxicity*

Substances

  • Caseins
  • Cyclohexenes
  • Environmental Pollutants
  • Vinyl Compounds
  • 4-vinyl-1-cyclohexene dioxide
  • Prolactin
  • Proto-Oncogene Proteins c-kit