title: Linoleic acid and antioxidants protect against DNA damage and apoptosis induced by palmitic acid.
abstract: Polyunsaturated fats are the main target for lipid peroxidation and subsequent formation of mutagenic metabolites, but diets high in saturated fats are more strongly associated with adverse health effects. We show that the common saturated fatty acid, palmitic acid, is a potent inducer of DNA damage in an insulin-secreting cell line, and in primary human fibroblasts. Damage is not associated with upregulation of inducible nitric oxide synthase, but is prevented by two different antioxidants, alpha-lipoic acid and 3,3'-methoxysalenMn(III) (EUK134), which also partly prevent palmitic acid-induced apoptosis and growth inhibition. Since mutagenic metabolites can be formed from peroxidation of polyunsaturated fatty acids, co-administration of palmitic and a polyunsaturated fatty acid might be particularly harmful. Palmitic acid-induced DNA damage is instead prevented by linoleic acid, which is acting here as a protective agent against oxidative stress, rather than as a source of mutagenic metabolites. These results illustrate the complexity of the relationship of dietary fat intake to genotoxicity.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockcroft Building, Lewes Road, Brighton BN2 4GJ, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Beeharry
authors.forename: Jillian E
authors.initials: JE
authors.lastname: Lowe
authors.forename: Alma Rosales
authors.initials: AR
authors.lastname: Hernandez
authors.forename: Julie A
authors.initials: JA
authors.lastname: Chambers
authors.forename: Flavia
authors.initials: F
authors.lastname: Fucassi
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cragg
authors.forename: Michael H L
authors.initials: MH
authors.lastname: Green
authors.forename: Irene C
authors.initials: IC
authors.lastname: Green
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects*; D004041:Dietary Fats / Q000009:adverse effects*; D005029:Ethylenediamines / Q000494:pharmacology; D005347:Fibroblasts; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology; D018384:Oxidative Stress; D019308:Palmitic Acid / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D012459:Salicylates / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004041:Dietary Fats; C433928:EUK-134; D005029:Ethylenediamines; D009942:Organometallic Compounds; D012459:Salicylates; D019308:Palmitic Acid; C011452:disalicylaldehyde ethylenediamine; D019787:Linoleic Acid