Cytochrome P450 monooxygenase eicosanoid pathway mediates the colon cancer-enhancing effects of dietary linoleic acid

CYP monooxygenase-mediated conversion of LA to EpOMEs plays critical roles in the health effects of dietary LA, implicating a unique mechanistic linkage between dietary fatty acid intake and cancer risks. Overall design: We determine the specific lipid metabolic pathways and metabolites involved in its colon cancer-enhancing effects. Using a LC-MS/MS-based lipidomics, we find that the previously unappreciated cytochrome P450 (CYP) monooxygenase pathway is a major pathway to metabolize LA in vivo. Furthermore, CYP monooxygenase is required for the colon cancer-promoting effects of LA, since LA-rich diet fails to exacerbate colon cancer in CYP monooxygenase-deficient mice.