Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers
article
Dietary omega-3 polyunsaturated fatty acids (ω-3 PUFAs) protect against photocarcinogenesis in animals, but prospective human studies are scarce. The mechanism(s) underlying the photoprotection are uncertain, although ω-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 ω-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/cm2 at baseline to 49 (16) mJ/cm2 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.
Chemicals/CAS: alpha tocopherol, 1406-18-4, 1406-70-8, 52225-20-4, 58-95-7, 59-02-9; ascorbic acid, 134-03-2, 15421-15-5, 50-81-7; glutathione, 70-18-8; icosapentaenoic acid, 25378-27-2, 32839-30-8; oleic acid, 112-80-1, 115-06-0; Ascorbic Acid, 50-81-7; DNA, 9007-49-2; Eicosapentaenoic Acid, 1553-41-9; Genetic Markers; Glutathione, 70-18-8; Oleic Acid, 112-80-1; Tumor Suppressor Protein p53; Vitamin E, 1406-18-4
Chemicals/CAS: alpha tocopherol, 1406-18-4, 1406-70-8, 52225-20-4, 58-95-7, 59-02-9; ascorbic acid, 134-03-2, 15421-15-5, 50-81-7; glutathione, 70-18-8; icosapentaenoic acid, 25378-27-2, 32839-30-8; oleic acid, 112-80-1, 115-06-0; Ascorbic Acid, 50-81-7; DNA, 9007-49-2; Eicosapentaenoic Acid, 1553-41-9; Genetic Markers; Glutathione, 70-18-8; Oleic Acid, 112-80-1; Tumor Suppressor Protein p53; Vitamin E, 1406-18-4
Topics
Physiological Sciences8 hydroxydeoxyguanosineAlpha tocopherolAntioxidantAscorbic acidGlutathioneIcosapentaenoic acidMonounsaturated fatty acidOleic acidOmega 3 fatty acidProtein p53AdultAgedCancer riskClinical trialComet assayControlled clinical trialControlled studyDNA damageDNA strand breakageDose responseDouble blind procedureDrug bioavailabilityDrug structureDrug tissue levelEpidermis cellErythemaFemaleFlatulenceGenotoxicityHumanHuman experimentHuman tissueImmunohistochemistryLipid peroxidationMaleNormal humanOxidative stressPeripheral lymphocytePhotooxidationPhotosensitivityPriority journalProtein expressionRandomized controlled trialReviewSkin cancerSkin carcinogenesisSunburnUltraviolet radiationAdultAgedAscorbic AcidBiological AvailabilityDietary SupplementsDNADNA DamageDNA RepairDouble-Blind MethodEicosapentaenoic AcidFemaleGenetic MarkersGlutathioneHumansLipid PeroxidationLymphocytesMaleMiddle AgedNeoplasms, Radiation-InducedOleic AcidSkinSkin NeoplasmsTumor Suppressor Protein p53Ultraviolet RaysVitamin E
TNO Identifier
237050
ISSN
01433334
Source
Carcinogenesis, 24(5), pp. 919-925.
Pages
919-925
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