Homer S. Black

Abstract Free radicals are chemical species characterized by an odd number of orbital electrons or by pairs of electrons of similar directional spin isolated singly in separate orbitals. Consequently most of these agents are highly reactive and usually exhibit an extremely short half‐life, although due to steric and resonance effects some exceptions occur. Some radicals and their precursors, such as the diradical O 2 which exists in the triplet state, represent a critical and essential element of normal metabolism of aerobic organisms where, under normal circumstances, controlled reduction of reactive oxygen species occurs via the cytochrome oxidase or cytochrome P‐450 mixed function monooxygenase systems. In addition to reactive oxygen species, organisms may be subjected to a wide‐range of other free radicals or their precursors, including those of both exogenous and endogenous origin. Elaborate defense mechanisms have evolved to avoid cellular damage from these highly reactive species. Enzymes, such as the superoxide dismutase, the glutathione peroxidase/reductase system, and catalase; interactions with conjugated diene systems such as those found in melanins, carotenoids, and tocopherols; and direct reduction by sulphydryl compounds, phenols, and purines represent but a few of these natural defense systems. Despite a strong rationale for considering free radicals as pathologic agents, progress in implicating these agents, or their reactions, in pathologic processes has been arduous. The fore‐most hurdle to providing definitive evidence for free radical involvement rests with the highly transient nature of these species, hardly reaching measurable levels in vivo and thereby making rigorous testing of the hypothesis extremely difficult. Indeed, free radical damage has been studied, for the most part, by indirect means–usually by measurement of known free radical reaction intermediates and products from which free radical involvement is implied. Nevertheless, free radical formation has been shown to occur in UV‐irradiated skin and a considerable body of circumstantial evidence has been amassed that strongly infers that these agents, or reactions initiated by them, are responsible for at least some of the deleterious effects of UV upon skin.

BACKGROUND: Actinic keratoses are premalignant lesions and are a sensitive and important manifestation of sun-induced skin damage. Studies in animals have shown that dietary fat influences the incidence of sun-induced skin cancer, but the effect of diet on the incidence of actinic keratosis in humans is not known. METHODS: We randomly assigned 76 patients with nonmelanoma skin cancer either to continue their usual diet (control group) or to eat a diet with 20 percent of total caloric intake as fat (dietary-intervention group). For 24 months, the patients were examined for the presence of new actinic keratoses by physicians unaware of their assigned diets. RESULTS: At base line, the mean (+/- SD) percentage of caloric intake as fat was 40 +/- 4 percent in the control group and 39 +/- 3 percent in the dietary-intervention group. After 4 months of dietary therapy the percentage of calories as fat had decreased to 21 percent in the dietary-intervention group, and it remained below this level throughout the 24-month study period. The percentage of calories as fat in the control group did not fall below 36 percent at any time. The cumulative number of new actinic keratoses per patient from months 4 through 24 was 10 +/- 13 in the control group and 3 +/- 7 in the dietary-intervention group (P = 0.001). CONCLUSIONS: In patients with a history of nonmelanoma skin cancer, a low-fat diet reduces the incidence of actinic keratosis.

Carotenoid pigments, particularly β-carotene and lycopene, are consumed in human foodstuffs and play a vital role in maintaining health. β-carotene is known to quench singlet oxygen and can have strong antioxidant activity. As such, it was proposed that β-carotene might reduce the risk of cancer. Epidemiological studies found inverse relationships between cancer risk and β-carotene intake or blood levels. However, clinical trials failed to support those findings and β-carotene supplementation actually increased lung cancer incidence in male smokers. Early experimental animal studies found dietary β-carotene inhibited UV-induced skin cancers. Later studies found that β-carotene supplementation exacerbated UV-carcinogenic expression. The discrepancies of these results were related to the type of diet the animals consumed. Lycopene has been associated with reduced risk of lethal stage prostate cancer. Other carotenoids, e.g., lutein and zeaxanthin, play a vital role in visual health. Numerous studies of molecular mechanisms to explain the carotenoids' mode of action have centered on singlet oxygen, as well as radical reactions. In cellular systems, singlet oxygen quenching by carotenoids has been reported but is more complex than in organic solvents. In dietary β-carotene supplement studies, damaging pro-oxidant reactivity can also arise. Reasons for this switch are likely due to the properties of the carotenoid radicals themselves. Understanding singlet oxygen reactions and the anti-/pro-oxidant roles of carotenoids are of importance to photosynthesis, vision and cancer.