Journal Article

Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers

Lesley E. Rhodes, Hassan Shahbakhti, Richard M. Azurdia, Ralf M.W. Moison, Marie-Jose S.T. Steenwinkel, Marie I. Homburg, Michael P. Dean, F. McArdle, Gerard M.J. Beijersbergen van Henegouwen, Bernd Epe and Arie A. Vink

in Carcinogenesis

Volume 24, issue 5, pages 919-925
Published in print May 2003 | ISSN: 0143-3334
Published online May 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg038
Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers

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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.

Keywords: CPD, cyclobutane pyrimidine dimers; EPA, eicosapentaenoic acid; MDA, malondialdehyde; MED, minimal erythemal dose; MM, malignant melanoma; ω-3 PUFAs, omega-3 polyunsaturated fatty acids; ROS, reactive oxygen species; SSB, single-strand breaks; TM, tail moment; UVR, ultraviolet radiation.

Journal Article.  6193 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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