Ontogeny of the major xenobiotic-metabolizing enzymes expression and the dietary lipids modulatory effect in the rat dimethylbenz(a)anthracene-induced breast cancer model

J Biochem Mol Toxicol. 2014 Dec;28(12):539-48. doi: 10.1002/jbt.21596. Epub 2014 Aug 28.

Abstract

Breast cancer is the most common malignancy in women worldwide. Environmental factors such as xenobiotic exposure and lifestyle and nutrition play a key role in its etiology. This study was designed to evaluate the age-related changes in the expression of major xenobiotic-metabolizing enzymes (XMEs) in the rat liver and the mammary gland in the dimethylbenz(a)anthracene-induced breast cancer model. The influence of dietary lipids on the ontogeny of XMEs was also evaluated. mRNA and protein levels of phase I (CYP1A1, CYP1A2, and CYP1B1) and phase II (NAD(P)H:quinone acceptor oxidoreductase 1 and GSTP1) enzymes were analyzed, as well as their regulation by AhR and Nrf2, respectively. Results showed differences in the phase I enzymes expression, whereas little changes were obtained in phase II. High corn oil and olive oil diets differentially influenced the expression of age-related changes, suggesting that the different susceptibility to xenobiotic exposure depending upon the age may be modulated by dietary factors.

Keywords: Breast Cancer Model; Dietary Lipids; Ontogeny; Polycyclic Aromatic Hydrocarbons (PAHs); Xenobiotic-Metabolizing Enzymes (XMEs).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity*
  • Aging / drug effects
  • Aging / metabolism
  • Aging / pathology
  • Animals
  • Aryl Hydrocarbon Hydroxylases / biosynthesis*
  • Carcinogens / toxicity*
  • Corn Oil / pharmacology*
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glutathione S-Transferase pi / biosynthesis*
  • Mammary Neoplasms, Animal / chemically induced
  • Mammary Neoplasms, Animal / enzymology
  • Mammary Neoplasms, Animal / pathology
  • NAD(P)H Dehydrogenase (Quinone) / biosynthesis*
  • NF-E2-Related Factor 2 / metabolism
  • Neoplasm Proteins / metabolism*
  • Olive Oil
  • Plant Oils / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Aryl Hydrocarbon / metabolism
  • Xenobiotics*

Substances

  • Carcinogens
  • NF-E2-Related Factor 2
  • Neoplasm Proteins
  • Nfe2l2 protein, rat
  • Olive Oil
  • Plant Oils
  • Receptors, Aryl Hydrocarbon
  • Xenobiotics
  • 9,10-Dimethyl-1,2-benzanthracene
  • Corn Oil
  • Aryl Hydrocarbon Hydroxylases
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, rat
  • Glutathione S-Transferase pi
  • Gstp1 protein, rat