Metabolism of exogenous and endogenous arachidonic acid in cancer.
Epidemiologic evidence in humans and controlled trials in animal models indicate that total dietary fat increases the risk of cancer. The animal evidence indicates that the greatest efficacy in promoting carcinogenesis is achieved with omega-6 fatty acids with little or no effect from either the omega-3 or monounsaturated fatty acid families. Epidemiologic studies in humans indicate a positive association between meat intake and colon cancer, but a negative association with chicken and fish. There is also a negative association between non-steroidal anti-inflammatory drug (NSAID) intake and colon cancer. Red meat is a potentially significant source of dietary arachidonic acid, which is the primary substrate for the eicosanoids whose production is blocked by NSAIDs. Thus there is a positive association between carcinogenesis and dietary intake of both the omega-6 fatty acid precursor linoleic acid and its product arachidonic acid, and a negative association with use of a drug blocking its metabolism to eicosanoids. Another potentially important factor in arachidonate metabolism is variation in its endogenous distribution. We have recently reported abnormal distribution of arachidonic acid between lipid fractions in human obesity, and parallel abnormalities in animal models of genetic obesity. This implies a potential role for variation in the endogenous distribution of arachidonic acid in the etiology of cancers which have increased incidence in human obesity. This paper addresses the role of arachidonate intake, its endogenous production, and its distribution within lipid fractions in carcinogenesis.
Phinney
S D
SD
Department of Internal Medicine, University of California at Davis 95616, USA.
D000818:Animals; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000378:metabolism*; D005227:Fatty Acids; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D009626:Terminology as Topic
D005227:Fatty Acids; D016718:Arachidonic Acid