title: Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers.
abstract: Dietary omega-3 polyunsaturated fatty acids (omega-3 PUFAs) protect against photocarcinogenesis in animals, but prospective human studies are scarce. The mechanism(s) underlying the photoprotection are uncertain, although omega-3 PUFAs may influence oxidative stress. We examined the effect of supplementation on a range of indicators of ultraviolet radiation (UVR)-induced DNA damage in humans, and assessed effect on basal and post-UVR oxidative status. In a double-blind randomized study, 42 healthy subjects took 4 g daily of purified omega-3 PUFA, eicosapentaenoic acid (EPA), or monounsaturated, oleic acid (OA), for 3 months. EPA was bioavailable; the skin content at 3 months showing an 8-fold rise from baseline, P < 0.01. No consistent pattern of alteration in basal and UVR-exposed skin content of the antioxidants glutathione, vitamins E and C or lipid peroxidation, was seen on supplementation. Sunburn sensitivity was reduced on EPA, the UVR-induced erythemal threshold rising from a mean of 36 (SD 10) mJ/cm(2) at baseline to 49 (16) mJ/cm(2) after supplementation, P < 0.01. Moreover, UVR-induced skin p53 expression, assessed immunohistochemically at 24 h post-UVR exposure, fell from a mean of 16 (SD 5) positive cells/100 epidermal cells at baseline to 8 (4) after EPA supplementation, P < 0.01. Peripheral blood lymphocytes (PBL) sampled on 3 successive days both pre- and post-supplementation, showed no change with respect to basal DNA single-strand breaks or oxidative base modification (8-oxo-dG). However, when susceptibility of PBL to ex vivo UVR was examined using the comet assay, this revealed a reduction in tail moment from 84.4 (SD 3.4) at baseline to 69.4 (3.1) after EPA, P = 0.03. No significant changes were seen in any of the above parameters following OA supplementation. Reduction in this range of early markers, i.e. sunburn, UVR-induced p53 in skin and strand breaks in PBL, indicate protection by dietary EPA against acute UVR-induced genotoxicity; longer-term supplementation might reduce skin cancer in humans.
authors.affiliation: Photobiology Unit, Dermatology Centre, University of Manchester, UK. lesley.e.rhodes@man.ac.uk
authors.forename: Lesley E
authors.initials: LE
authors.lastname: Rhodes
authors.forename: Hassan
authors.initials: H
authors.lastname: Shahbakhti
authors.forename: Richard M
authors.initials: RM
authors.lastname: Azurdia
authors.forename: Ralf M W
authors.initials: RM
authors.lastname: Moison
authors.forename: Marie-Jose S T
authors.initials: MJ
authors.lastname: Steenwinkel
authors.forename: Marie I
authors.initials: MI
authors.lastname: Homburg
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dean
authors.forename: F
authors.initials: F
authors.lastname: McArdle
authors.forename: Gerard M J
authors.initials: GM
authors.lastname: Beijersbergen van Henegouwen
authors.forename: Bernd
authors.initials: B
authors.lastname: Epe
authors.forename: Arie A
authors.initials: AA
authors.lastname: Vink
mesh_terms: D000328:Adult; D000368:Aged; D001205:Ascorbic Acid / Q000378:metabolism; D001682:Biological Availability; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D019587:Dietary Supplements; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D005819:Genetic Markers; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008214:Lymphocytes / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000517:prevention & control*; D019301:Oleic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000235:genetics / Q000517:prevention & control*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000378:metabolism
chemical_list: D005819:Genetic Markers; D016159:Tumor Suppressor Protein p53; D014810:Vitamin E; D019301:Oleic Acid; D004247:DNA; D015118:Eicosapentaenoic Acid; D005978:Glutathione; D001205:Ascorbic Acid