Prepubertal octylphenol exposure up-regulate BRCA1 expression, down-regulate ERalpha expression and reduce rat mammary tumorigenesis

Cancer Epidemiol. 2009 Jul;33(1):51-5. doi: 10.1016/j.canep.2009.04.017. Epub 2009 May 27.

Abstract

Background: Endogenous estrogens play an important role in the development of breast cancer. Octylphenol (OP) and genistein (GEN) are estrogen-like chemicals. Prepubertal estradiol and genistein exposure can up-regulate BRCA1 mRNA in mammary gland and reduce futuer breast cancer risk. In the present study, the effects of prepubertal exposure to high-dose OP and GEN on mammary carcinogenesis and the association with the expression of BRCA1 and ERalpha were investigated.

Methods: Prepubertal female Sprague-Dawley rats were exposed to 20, 40, 80mg/kg OP daily from postnatal day (PND) 22-28, subsequently, the rats were given a single dose of 100mg/kg 7,12-dimethylbenz [a] anthracene (DMBA) on PND42 to induce mammary tumor.

Results: The incidence of DMBA-induced mammary tumors significantly decreased when rats were treated with 40mg/kg OP. BRCA1 mRNA and protein expression were found up-regulated and ERalpha expression was down-regulated in the mammary tumor when rats were exposed to 40mg/kg octylphenol.

Conclusion: Exposure 40mg/kg octylphenol can reduce later breast cancer risk in prepubertal Sprague-Dawley rats, the protective effect of OP is associated with persistent up-regulation of BRCA1 and down-regulation of ERalpha in the mammary tumor.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • BRCA1 Protein / genetics*
  • BRCA1 Protein / metabolism
  • Down-Regulation
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Genistein / pharmacology*
  • Mammary Neoplasms, Animal / genetics
  • Mammary Neoplasms, Animal / metabolism
  • Mammary Neoplasms, Animal / prevention & control*
  • Phenols / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation

Substances

  • Anticarcinogenic Agents
  • BRCA1 Protein
  • Estrogen Receptor alpha
  • Phenols
  • RNA, Messenger
  • octylphenol
  • 9,10-Dimethyl-1,2-benzanthracene
  • Genistein