Reassessment of a free radical theory of cancer with emphasis on ultraviolet carcinogenesis.
Pro-oxidants, reactive species and free radicals, are toxic substances that can cause oxidative damage to major constituents of biological systems. In contradistinction, antioxidants are defined as any substance that significantly prevents the pro-oxidant-initiated oxidation of a substrate. Consequently, it was suggested that it might be possible to reduce free radical damage and thus cancer risk through 3 dietary changes: (1) caloric reduction, that is, lowering the level of free radical reactions arising in the course of normal metabolism; (2) minimize dietary components that increase the level of free radical reactions (eg, polyunsaturated fats); and (3) supplement the diet with one or more free radical reaction inhibitors (antioxidants). Lipid peroxidation exemplifies the type of chain reaction initiated by free radicals in (2) and (3). Both the phenolic antioxidant butylated hydroxytoluene (BHT) and the carotenoid beta-carotene can terminate such reactions and have been shown to influence ultraviolet (UV) carcinogenesis. However, there is a lack of correlation between physicochemical and patho-physiological responses in both instances. Whereas the influence on UV carcinogenesis of both antioxidants has been reported to diminish as the level of dietary fat decreases, pointing to the involvement of lipid peroxidative reactions, the mode of BHT's action in inhibiting UV carcinogenesis appears to be related to UV dose diminution through increased spectral absorbance of the stratum corneum. beta-carotene has no such effect and may actually exacerbate UV carcinogenesis under certain dietary conditions. This paradox points to the complex relationship between chemical mechanisms and biological mode of action of antioxidants. Recent clinical and experimental data suggest that antioxidant supplementation of the complex and intricately balanced natural antioxidant defense system as a cancer prevention strategy will demand extreme caution.
Black
Homer S
HS
Department of Dermatology, Baylor College of Medicine, Houston, Texas, USA. hblack@bcm.tmc.edu
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019033:Delivery of Health Care, Integrated; D005609:Free Radicals / Q000009:adverse effects / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*; D051379:Mice; D009369:Neoplasms / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D018384:Oxidative Stress; D011322:Primary Prevention / Q000379:methods; D011379:Prognosis; D051381:Rats; D012307:Risk Factors; D012878:Skin Neoplasms / Q000209:etiology / Q000517:prevention & control; D014466:Ultraviolet Rays / Q000009:adverse effects*; D019207:beta Carotene / Q000494:pharmacology
D000975:Antioxidants; D005609:Free Radicals; D019207:beta Carotene