Dietary lipids differentially modulate the initiation of experimental breast carcinogenesis through their influence on hepatic xenobiotic metabolism and DNA damage in the mammary gland

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 1 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. Summary: 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. (C) 2017 Elsevier Inc. All rights reserved.