title: Dietary lipids differentially modulate the initiation of experimental breast carcinogenesis through their influence on hepatic xenobiotic metabolism and DNA damage in the mammary gland.
abstract: Breast cancer is the most common malignancy among women worldwide. In addition to reproductive factors, environmental factors such as nutrition and xenobiotic exposure have a role in the etiology of this malignancy. A stimulating and a potentially protective effect on experimental breast cancer has been previously described for high corn oil and high extra-virgin olive oil diets, respectively. This work investigates the effect of these lipids on the metabolism of 7,12-dimethylbenz(a)anthracene (DMBA), a polycyclic aromatic hydrocarbon that can initiate carcinogenesis and its consequences in an experimental rat breast cancer model. The PUFA n-6-enriched diet increased expression of Phase I enzymes prior to DMBA administration and raised the activity of CYP1s in the hours immediately after induction, while reducing the activity of Phase II enzymes, mainly NQO1. The levels of reactive metabolites measured in plasma by GC-MS and DMBA-DNA adducts in the mammary gland of the animals fed the high corn oil diet were also higher than in the other groups. On the other hand, the high extra-virgin olive oil diet and the control low-fat diet exhibited better coordinated Phase I and Phase II activity, with a lower production of reactive metabolites and less DNA damage in the mammary gland. The concordance between these effects and the different efficacy of the carcinogenesis process due to the dietary treatment suggest that lipids may differently modify mammary gland susceptibility or resistance to cancer initiation over the exposure to environmental carcinogens.
  
  
  
  Dietary lipids influence the initiation of DMBA-induced mammary cancer through the modulation of liver xenobiotic metabolism, formation of reactive metabolites and subsequent DNA damage in the target tissue.
authors.affiliation: Medical Physiology Unit, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Manzanares
authors.affiliation: Medical Physiology Unit, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: de Miguel
authors.affiliation: Department of Statistics, Universitat de Barcelona, 08028 Barcelona, Spain.
authors.forename: M Carme
authors.initials: MC
authors.lastname: Ruiz de Villa
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.affiliation: Medical Physiology Unit, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Escrich
authors.affiliation: Medical Physiology Unit, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. Electronic address: Montserrat.Solanas@uab.es.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Solanas
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000097:blood / Q000633:toxicity; D000818:Animals; D003314:Corn Oil / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects*; D019587:Dietary Supplements; D005260:Female; D008658:Inactivation, Metabolic / Q000187:drug effects* / Q000235:genetics; D008055:Lipids / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D000069463:Olive Oil / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D015262:Xenobiotics / Q000493:pharmacokinetics*
chemical_list: D008055:Lipids; D000069463:Olive Oil; D015262:Xenobiotics; D015127:9,10-Dimethyl-1,2-benzanthracene; D003314:Corn Oil; C585499:Cyp1b1 protein, rat; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat
keywords: Breast cancer initiation; DMBA; Dietary lipids; Olive oil; PUFA N-6; Xenobiotic metabolism