Dietary clofibrate stimulates the formation and size of estradiol-induced breast tumors in female August-Copenhagen Irish (ACI) rats

Sonia Mesia-Vela, Rosa I. Sanchez, Kathleen G. Roberts, Kenneth R. Reuhl, Allan H. Conney, Frederick C. Kauffman

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Administration of 0.4% clofibrate in the diet stimulated estradiol (E2)-induced mammary carcinogenesis in the August-Copenhagen Irish (ACI) rat without having an effect on serum levels of E2. This treatment stimulated by several-fold the NAD(P)H-dependent oxidative metabolism of E2 and oleyl-CoA-dependent esterification of E2 to 17β-oleyl-estradiol by liver microsomes. Glucuronidation of E2 by microsomal glucuronosyltransferase was increased moderately. In contrast, the activity of NAD(P)H quinone reductase 1 (NQO1), a representative monofunctional phase 2 enzyme, was significantly decreased in liver cytosol of rats fed clofibrate. Decreases in hepatic NQO1 in livers of animals fed clofibrate were noted before the appearance of mammary tumors. E2 was delivered in cholesterol pellets implanted in 7-8-week-old female ACI rats. The animals received AIN-76A diet containing 0.4% clofibrate for 6, 12 or 28 weeks. Control animals received AIN-76A diet. Dietary clofibrate increased the number and size of palpable mammary tumors but did not alter the histopathology of the E2-induced mammary adenocarcinomas. Collectively, these results suggest that the stimulatory effect of clofibrate on hepatic esterification of E2 with fatty acids coupled with the inhibition of protective phase 2 enzymes, may in part, enhance E2-dependent mammary carcinogenesis in the ACI rat model.

Original languageEnglish (US)
Pages (from-to)63-72
Number of pages10
JournalToxicology
Volume246
Issue number1
DOIs
StatePublished - Apr 3 2008

All Science Journal Classification (ASJC) codes

  • Toxicology

Keywords

  • Breast cancer
  • Clofibrate (2-(4-chlorophenoxy)-2-methyl-propanoic acid
  • Estradiol
  • ethyl ester)

Fingerprint Dive into the research topics of 'Dietary clofibrate stimulates the formation and size of estradiol-induced breast tumors in female August-Copenhagen Irish (ACI) rats'. Together they form a unique fingerprint.

  • Cite this