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

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.