Dietary extra-virgin olive oil and corn oil differentially modulate the mRNA expression of xenobiotic-metabolizing enzymes in the liver and in the mammary gland in a rat chemically induced breast cancer model.
High extra-virgin olive oil (EVOO) and corn oil diets differentially modulate experimental mammary carcinogenesis. We have investigated their influence on the initiation stage through the modulation of the expression of xenobiotic-metabolizing enzymes (XMEs) in the liver and the mammary gland. Female Sprague-Dawley rats were fed a low-fat (LF), high corn oil (HCO), or high EVOO (HOO) diet from weaning and gavaged with 7,12-dimethylbenz(a)anthracene (DMBA). The HCO diet increased the mRNA levels of the phase I enzymes CYP1A1, CYP1A2 and, to a lesser extent, CYP1B1, in the liver. The Aryl hydrocarbon receptor (AhR) seemed to be involved in this upregulated CYP1 expression. However, a slight trend toward an increase in the mRNA levels of the phase II enzymes GSTP1 and NQO1 was observed with the HOO diet. At least in the case of GSTP1, this effect was linked to an increased Nrf2 transactivation activity. This different regulation of the XMEs expression led, in the case of the HCO diet, to a balance between the production of active carcinogenic compounds and their inactivation tilted toward phase I, which would stimulate DMBA-induced cancer initiation, whereas the HOO diet was associated with a slower phase I metabolism accompanied by a faster phase II detoxification, thus reducing the output of the active compounds to the target tissues. In the mammary gland, the differential effects of diets may be conditioned by the state of cell differentiation, sexual maturity, and hormone metabolism.
aDepartment of Cell Biology, Physiology and Immunology, Medical Physiology Unit, School of Medicine, Universitat Autònoma de Barcelona, Barcelona bDepartment of Pathology, Corporació Sanitària Parc Taulí, Sabadell, Spain.
Miguel Á
MÁ
Manzanares
Montserrat
M
Solanas
Raquel
R
Moral
Raquel
R
Escrich
Elena
E
Vela
Irmgard
I
Costa
Eduard
E
Escrich
D000818:Animals; D003314:Corn Oil / Q000008:administration & dosage* / Q000009:adverse effects; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000201:enzymology*; D042361:Mammary Glands, Human / Q000201:enzymology*; D008325:Mammary Neoplasms, Experimental / Q000178:diet therapy / Q000201:enzymology* / Q000209:etiology; D000069463:Olive Oil / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015262:Xenobiotics / Q000009:adverse effects / Q000378:metabolism
D004042:Dietary Fats, Unsaturated; D000069463:Olive Oil; D012333:RNA, Messenger; D015262:Xenobiotics; D003314:Corn Oil