Ontogeny of the Major Xenobiotic-Metabolizing Enzymes Expression and the Dietary Lipids Modulatory Effect in the Rat Dimethylbenz(a)anthracene-Induced Breast Cancer Model

• Published in: Journal of biochemical and molecular toxicology 2014-12, Vol.28 (12), p.539-548
• Main Authors: Manzanares, Miguel Ángel, Solanas, Montserrat, Moral, Raquel, Escrich, Raquel, Vela, Elena, Escrich, Eduard
• Format: Article
• Language: English
• Subjects: 9,10-Dimethyl-1,2-benzanthracene - toxicity; Aging - drug effects; Aging - metabolism; Aging - pathology; Animals; Aryl Hydrocarbon Hydroxylases - biosynthesis; Breast cancer; Breast Cancer Model; Carcinogens - toxicity; Corn Oil - pharmacology; Dietary Lipids; Enzymes; 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; Neoplasm Proteins - metabolism; NF-E2-Related Factor 2 - metabolism; Olea; Olive Oil; Ontogeny; Plant Oils - pharmacology; Polycyclic Aromatic Hydrocarbons (PAHs); Rats; Rats, Sprague-Dawley; Receptors, Aryl Hydrocarbon - metabolism; Rodents; Xenobiotic-Metabolizing Enzymes (XMEs); Xenobiotics
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.21596

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.