Carcinogenesis – EPA on UVR-related Cancer Risk in Humans

1. Lesley E. Rhodes1,2,6, 
2. Hassan Shahbakhti1,2, 
3. Richard M. Azurdia2,
4. Ralf M.W. Moison3, 
5. Marie-Jose S.T. Steenwinkel4, 
6. Marie I. Homburg5,
7. Michael P. Dean1,2, 
8. F. McArdle2, 
9. Gerard M.J. Beijersbergen van Henegouwen3,
10. Bernd Epe5 and 
11. Arie A. Vink4

1. ¹Photobiology Unit, Dermatology Centre, University of Manchester, Manchester, UK
2. ²Department of Dermatology/Medicine, Royal Liverpool University Hospital and University of Liverpool, Liverpool, UK
3. ³Department of Medicinal Photochemistry, Leiden/Amsterdam Centre for Drug Research, Leiden University, The Netherlands
4. ⁴TNO Nutrition and Food Research, Zeist, The Netherlands
5. ⁵University of Mainz, Mainz, Germany

 

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Abstract

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.