[Frontiers in Bioscience, Scholar, 7, 30-39, June 1, 2015]

The role of nutritional lipids and antioxidants in UV-induced skin cancer

Homer S. Black 1

1Department of Dermatology, Baylor College of Medicine, Houston, Texas, 77030, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Dietary lipids
    3.1. Experimental
    3.2. Clinical
4. Antioxidants
    4.1. Butylated hydroxytoluene
    4.2. Beta-carotene
5. Conclusions
6. Acknowledgements
7. References

1. ABSTRACT

Two dietary tenets of the free radical theory of cancer require refinement. The first was dietary reduction of vulnerable free-radical targets, e.g., polyunsaturated lipids. The second was the addition of one or more antioxidants to the diet. Further, it was reported in 1939 that high levels of dietary fat exacerbated UV-carcinogenesis. Both lines of enquiry (dietary lipid and antioxidant effects on UV-carcinogenesis) were investigated. Both dietary lipids and antioxidants modified carcinogenic expression. Increasing levels of omega-6 polyunsaturated fatty acids (PUFA) exacerbated UV-carcinogenesis. However, omega-3 PUFA dramatically inhibited carcinogenic expression. It is probable that the action of omega-6 and-3 PUFA rests with differential metabolic intermediates, both tumor promoting and immune-modulating, that each PUFA generates through lipoxygenase and cyclooxygenase pathways. Antioxidant supplementation with butylated hydroxytoluene or beta-carotene demonstrated that each exerted its own specific antioxidant mechanism(s). When introduced into the complex milieu of the cell with its own intricate and complex antioxidant defense system, detrimental effects may ensue. These results point to oversimplification of these dietary suggestions to reduce cancer risk and the necessity to refine these dietary recommendations.

7. REFERENCES

1. C. A. Baumann, and H. P. Rusch. Effect of diet on tumors induced by ultraviolet light. Am. J. Cancer 35: 213-221 (1939)

2. H. S. Black. Skin Cancer. In: Nutritional Oncology. 2nd Edition. D. Heber, G. L. Blackburn, V. L. W. Go, J. Milner, Eds) Elsevier, San Diego, Ca. 405-422 (2006)

3. D. Harman. Role of free radicals in mutation, cancer, aging, and the maintenance of life. Radiat. Res. 16: 753-763 (1962)
DOI: 10.2307/3571274

4. D. Harman. The free radical theory of aging. In: Free Radicals in Biology, Pryor, WA (Ed.) Academic Press, NY, USA, 255-275 (1982)
DOI: 10.1016/B978-0-12-566505-6.50015-6

5. A. L. Norins. Free radical formation in the skin following exposure to ultraviolet light. J. Invest. Dermatol. 39: 445-448 (1962)
DOI: 10.1038/jid.1962.65
DOI: 10.1038/jid.1962.137

6. H. S. Black. Potential involvement of free radical reactions in ultraviolet light-mediated cutaneous damage. Photochem. Photobiol. 46: 213-221 (1987)
DOI: 10.1111/j.1751-1097.1987.tb04759.x

7. .H.S. Black, W. Lenger, V. McCann, J. Thronby. Relation of UV dose to antioxidant modification of photocarcinogenesis. J. Am. Coll. Toxicol. 2: 201–207 (1983)
DOI: 10.3109/10915818309140682

8. H. S. Black, W. A. Lenger, J. Gerguis, J. I. Thornby. Relation of antioxidants and level of dietary lipid to epidermal lipid peroxidation and ultraviolet carcinogenesis. Cancer Res. 45: 6254-6259 (1985)

9. H.S. Black. Effects of dietary antioxidants on actinic tumor induction. Res. Commun. Chem. Pathol. Pharmacol. 7: 783-786 (1974)

10. H. S. Black, W. Lenger, A. W. Phelps and J. I. Thornby. Influence of dietary lipid upon ultraviolet-light carcinogenesis. Nutr. Cancer 5: 59-68 (1983)
DOI: 10.1080/01635588309513780

11. R.C.S. Barcelos, L.T. Vey, H.J.Segal, K. Roversi, Kr. Roverski, V. T. Dias, F. Trevizol, F. T. Kuhn, G. S. Dolci, C. S. Pase, J. Piccole, J. C. Veit, T. Emanuelli, S. C. A. Luiz, and M. E. Burger. Cross-generational trans fat intake exacerbates UV radiation-induced damage in rat skin. Food Chem. Toxicol. 69: 38-45 (2014)
DOI: 10.1016/j.fct.2014.03.031

12. I. F. Orengo, H. S. Black, A. H. Kettler, J. E. Jr. Wolf. Influence of dietary menhaden oil upon carcinogenesis and various cutaneous responses to ultraviolet radiation. Photochem. Photobiol. 49: 71-77 (1989)
DOI: 10.1111/j.1751-1097.1989.tb04080.x

13. M. A. Fischer and H. S. Black. Modification of membrane composition, eicosanoid metabolism, and immunoresponsiveness by dietary omega-3 and omega-6 fatty acid sources, modulators of ultraviolet-carcinogenesis. Photochem. Photobiol. 54: 381-387 (1991)

14. H. S. Black, G. Okotie-Eboh, G. Gerguis, J. I. Urban, and J. I. Thornby. Dietary fat modulates immunoresponsiveness in UV-irradiated mice. Photochem. Photobiol. 62: 964-969 (1995)

15. H.S. Black and, L. E. Rhodes. The potential of omega-3 fatty acids in the prevention of non-melanoma skin cancer. Cancer Detect. Prev. 30: 224-232 (2006)
DOI: 10.1016/j.cdp.2006.04.008

16. H. S. Black. Omega-3 fatty acids and non-melanoma skin cancer. In: Handbook of Diet, Nutrition, and the Skin. Preedy VR (Ed.) Wageningen Academic Publishers, The Netherlands 367-378 (2012)
DOI: 10.3920/978-90-8686-729-5_22

17. H. S. Black, J. I. Thornby, J. Gerguis, W. Lenger. Influence of dietary omega-6, -3 fatty acid sources on the initiation and promotion stages of photocarcinogenesis. Photochem. Photobiol. 56: 195-199 (1992)
DOI: 10.1111/j.1751-1097.1992.tb02147.x

18. H. S. Black, J. A.Herd, L. H. Goldberg, J. E.Wolf, J. I. Thornby, T. Rosen, D. Bruce, J. A. Tschen, J. P. Foreyt, L. W. Scott, S. Jaax. Effect of a low-fat diet on the incidence of actinic keratosis. N Engl J Med 330: 1272-1275 (1994)
DOI: 10.1056/NEJM199405053301804

19. H. S. Black, J. I. Thornby, J. E. Wolf, L. H. Goldberg, J. A. Herd, T. Rosen, S. Bruce, J.A. Tschen, L. W. Scott, S. Jaax, J. P. Foreyt, B. Reusser. Evidence that a low-fat diet reduces the occurrence of non-melanoma skin cancer. Int J Cancer 62: 165-169 (1995)
DOI: 10.1002/ijc.2910620210

20. S. Jaax, L. W. Scott, J. E. Wolf, J. I. Thornby, H. S. Black. General guidelines for a low-fat diet effective in the management and prevention of nonmelanoma skin cancer. Nutr Cancer 27: 150-156 (1997)
DOI: 10.1080/01635589709514517

21. L. E. Rhodes, H. Shahbakhti, R. M. Azurdia, R. M. Moison, M. J. Steenwinkel, M. I. Homburg, M. P. Dean, F. McArdle, G. M. J. Beijersbergen van Henegouwen, B. Epe, A. A. Vink. Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers. Carcinogenesis 24: 919-925 (2003)
DOI: 10.1093/carcin/bgg038

22. I. A. Hakim, R. B. Harris, C. Ritenbaugh. Fat intake and risk of squamous cell carcinoma of the skin. Nutr Cancer 36: 155-162 (2000)
DOI: 10.1207/S15327914NC3602_3

23. S. E. Noel, A. C. S. Stoneham, C. M. Olsen, L. E. Rhodes, A. C. Green. Consumption of omega-3 fatty acids and the risk of skin cancers: A systematic review and meta-analysis. Int. J. Cancer, 135: 149–156 (2014)

24. H. S. Black, L. E. Rhodes. The potential of omega-3 fatty acids in the prevention of non-melanoma skin cancer. Cancer Detection and Prevention 30: 224-232 (2006)
DOI: 10.1667/0033-7587(2001)156[0036:DEAPSI]2.0.CO;2

25. R. Moison, G. Beijersbergen Van Henegouwen. Dietary eicosapentaenoic acid prevents systemic immunosuppression in mice induced by UVB radiation. Radiat Res 156: 36-44 (2001)
DOI: 10.3945/ajcn.112.049494

26. S. M. Pilkington, K. A. Massey, S. P. Bennett, N. M. Al-Aasswad, K. Roshdy, N. K. Gibbs, P. S. Friedmann, A. Nicolaou, L. E. Rhodes. Randomized controlled trial of oral omega-3 PUFA in solar-simulated radiation-induced suppression of human cutaneous immune responses. Am J Clin Nutr 97: 646-652 (2013)

27. H. S. Black. Nutritional lipid and antioxidant supplements: risks versus benefits. Expert Rev Dermatol 7: 483-492 (2012).
DOI: 10.1111/1523-1747.ep12607661

28. H. S. Black and J. T. Chan. Suppression of ultraviolet light induced tumor formation by dietary antioxidants. J. Invest. Dermatol. 65: 412-414 (1975)

29. H. S. Black, J. T. Chan, G. E. Brown. Effects of dietary constituents on ultraviolet light-mediated carcinogenesis. Cancer Res. 38: 1384-1387 (1978)

30. L. Pauling, R. Willoughby, R. Reynolds, B. E. Blaisdell, S. Lawson. Incidence of squamous cell carcinoma in hairless mice irradiated with ultraviolet light in relation to intake of ascorbic acid (vitamin C) and DL-alpha-tocopheryl acetate (vitamin E) Int. J. Nutr. Res. 23: 53-82 (1982)

31. H. S. Black, C. M. Kleinhans, H. T. Hudson, R. M. Sayre, P. P. Agin. Studies on the mechanism of protection by butylated hydroxytoluene to UV-radiation damage. Photobiochem. Photobiophys. 1: 119-123 (1980)
DOI: 10.1111/1523-1747.ep12524440

32. M. D. Koone and H. S. Black. A mode of action for butylated hydroxytoluene-mediated photoprotection. J. Invest. Dermatol. 87: 343-347 (1986)
DOI: 10.1111/1523-1747.ep12258527

33. G. De Rios, J. T. Chan, H. S. Black, A. H. Rudolph, J. M. Know. Systemic protection by antioxidants against UVL-induced erythema. J. Invest. Dermatol. 70: 123-125 (1978)
DOI: 10.1111/1523-1747.ep12523686

34. A. O. Peterson, V. McCann, H. S. Black. Dietary modification of UV-induced epidermal ornithine decarboxylase. J. Invest. Dermatol. 75: 408-410. (1980)

35. H. S. Black and J. Gerguis. Use of the Ames Test in assessing the relation of dietary lipid and antioxidants on N-2-fluorenylacetamide activation. J. Environ. Pathol. Toxicol. 4: 131-138 (1980)
DOI: 10.1126/science.6710156

36. G. W. Burton and K. U. Ingold. Beta-carotene: an unusual type of lipid antioxidant. Science 224: 569-573 (1984)

37. H. S. Black and C. R. Lambert. Radical reactions of carotenoids and potential influence on UV carcinogenesis. Curr. Probl. Dermatol. 29: 140-146 (2001)
DOI: 10.1038/290201a0

38. R. Peto, R. Doll, J. D. Buckley, M. B. Sporn. Can dietary beta-carotene materially reduce human cancer rates? Nature290: 201-208 (1981)
DOI: 10.1159/000225601

39. M. M. Mathews-Roth. Antitumor activity of beta-carotene, canthaxanthin and phytoene. Oncology 39: 33-37 (1982)
DOI: 10.1111/j.1751-1097.1985.tb03544.x

40. M. M. Mathews-Roth and N. I. Krinsky. Carotenoid dose level and protection against UV-B induced skin tumors. Photochem. Photobiol. 42: 35-38 (1985)
DOI: 10.1056/NEJM199009203231204

41. E. R. Greenberg, J. A. Baron, T. A. Stukel, M. M. Stevens, J. S. Mandel, S. K. Spencer, P. M. Elias, N. Lowe, D. W. Nierenberg, G. Bayrd, J. C. Vance, D. H. Freeman, W. E. Clendenning, T. Kwan, and the Skin Cancer Prevention Study Group. A clinical trial of beta-carotene to prevent basal-cell and squamous-cell cancers of the skin. N. Engl. J. Med. 323: 789 – 795 (1990)

42. The alpha-tocopherol, Beta-carotene Cancer Prevention Study Group. The effect of vitamin E and beta-carotene on the incidence of lung cancer and other cancers in male smokers. N. Engl. J. Med. 330: 1029-1035 (1996)
DOI: 10.1080/01635589809514705

43. H. S. Black. Radical interception by carotenoids and effects on UV carcinogenesis. Nutr. Cancer 31: 173-178 (1998)
DOI: 10.1207/S15327914NC372_9

44. H. S. Black, G. Okotie-Eboh, J. Gerguis. Diet potentiates the UV-carcinogenic response to beta-carotene. Nutr. Cancer 37: 173-178 (2000)
DOI: 10.1016/S1011-1344(96)07299-5

45. T. G. Truscott. Beta-carotene and disease: a suggested pro-oxidant and anti-oxidant mechanism and speculations concerning its role in cigarette smoking. J. Photochem. Photobiol B. 35: 233 – 235 (1996)

46. R. Edge and T. G. Truscott. Carotenoids – free radical reactions. Spectrum 13: 12-20 (2000)
DOI: 10.1021/ja953181r

47. J. H. Tinkler, S. M. Tavender, A. W. Parker, D.J. McGarvey, l. Mulroy, T. G. Truscott. Investigation of carotenoid radicals and triplet states by laser flash photolysis and time-resolved Resonance Raman Spectroscopy: Observation of competitive energy and electron transfer. J. Am. Chem. Soc.118: 1756 - 1761 (1996)
DOI: 10.1021/ja974191q

48. R. Edge, E. J. Land, D. McGarvey, L. Mulroy, T. G. Truscott. Relative one-electron reduction potentials of carotenoid radical cations and the interactions of carotenoids with the vitamin E radical cation. J. Am. Chem. Soc. 120: 4087 – 4090 (1997)
DOI: 10.1207/S15327914NC4501_5

49. H. S. Black, J. Gerguis. Modulation of vitamins E and C fails to ameliorate beta-carotene exacerbation of UV-carcinogenesis in mice. Nutr. Cancer 45: 36-45 (2003)
DOI: 10.3109/03630269.2010.485873

50. H. S. Black. Interaction of ascorbic acid and tocopherol on beta-carotene modulated carcinogenesis. Hemoglobin 34: 284-290 (2010)
DOI: 10.1021/jo00065a013

51. W. A. Pryor, J. A. Cornicelli, L. J. Devall, B. Tait, B. K. Trivedi, B. T. Witiak, M. Wu. A rapid screening test to determine the antioxidant potencies of natural and synthetic antioxidants. J. Org. Chem. 58: 3521 - 3532 (1993)

52. H. S. Black. Antioxidant supplementation: Revisited. J. Integr. Oncol. 1: 2 (2012) 1:e103.
DOI: 10:4172/2329-6771. 100e103.

53. IARC Working Group on the Evaluation of Cancer Prevention Agents. IARC Handbook of Cancer Prevention. Carotenoids. Vol. 2, Lyon, France (1998)

54. World Cancer Research Fund/American Institute for Cancer Research, Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. AICR, Washington, DC, USA (2007)
DOI: 10.1586/edm.12.41s

55. H. S. Black. Nutritional lipid and antioxidant supplements: risks versus benefits. Expert. Rev. Dermatol. 7: 483-492 (2012)

Key Words: Dietary Lipids, Skin Cancer, Ultraviolet Carcinogenesis, Antioxidants, Beta-Carotene, Butylated Hydroxytoluene, Review

Send correspondence to: Homer S. Black, Department of Dermatology, Baylor College of Medicine, Houston, Texas, 77030, USA, Tel:713-785-1887, E-mail: hblack@bcm.tmc.edu E-mail:fbs@bioscience.org