Black Homer S, Gerguis Janette
Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX 77030, USA.
Nutr Cancer. 2003;45(1):36-45. doi: 10.1207/S15327914NC4501_5.
b-Carotene is a strong singlet oxygen quencher and, under most conditions, exhibits strong antioxidant properties. Based on these properties, and a number of epidemiological studies, it was suggested that an above average intake of the carotenoid might reduce cancer risks. Earlier studies had found that b-carotene, when added to commercial closed-formula rodent diets, provided significant photoprotection to ultraviolet light (UV) carcinogenesis. However, clinical trials found that b-carotene supplementation evoked no change in incidence of nonmelanoma skin cancer and that smokers suffered a significant increase in lung cancer incidence. Further, recent studies, employing b-carotene-supplemented semidefined diets, not only failed to find a photoprotective effect, but significant exacerbation of UV carcinogenic expression resulted. Based on the relative electron transfer rate constants for interactions between b-carotene, a-tocopherol (vitamin E), and vitamin C, a mechanism was proposed for the repair of b-carotene radical cation, a strongly oxidizing radical resulting from b-carotene interactions with many oxidizing species. It was theorized that vitamin C repaired the carotenoid radical cation. As mice have no nutritional requirement for vitamin C and smokers are known to exhibit low levels of the vitamin, it was suggested that differences in the relative levels of vitamin C in closed-formula rations (no vitamin C) in which photoprotection occurred, and semidefined diets (containing vitamin C) in which exacerbation resulted, might account for the differences in response. Hairless mice were fed b-carotene-supplemented semidefined diets containing varying levels of vitamins E and C (either increasing their concentrations or reducing them to reflect levels found in closed-formula rations) and subjected to a UV carcinogenesis protocol. Increasing levels of vitamins E and C did not ameliorate b-carotene exacerbation of UV carcinogenesis. Nor did elimination of vitamin C from the diet. Reduced levels of dietary vitamin E augmented b-carotene exacerbation of UV carcinogenic expression, suggesting vitamin E and b-carotene interaction. It is concluded that the photoprotective effect of b-carotene reported earlier by others, or the noninjurious effect of b-carotene found in our studies with closed-formula rations, might depend on interaction with other dietary factors that are either absent, or present in ineffectual concentrations, in the semidefined diet in which exacerbation of UV carcinogenesis occurs. Those factors could be other carotenoids, their isomers, or some yet unidentified phytochemical(s).
β-胡萝卜素是一种强效的单线态氧猝灭剂，在大多数情况下都具有很强的抗氧化特性。基于这些特性以及一些流行病学研究，有人提出摄入高于平均水平的类胡萝卜素可能会降低患癌风险。早期研究发现，将β-胡萝卜素添加到商业封闭式配方啮齿动物饲料中，能为紫外线（UV）致癌作用提供显著的光保护。然而，临床试验发现补充β-胡萝卜素并未改变非黑色素瘤皮肤癌的发病率，且吸烟者的肺癌发病率显著增加。此外，最近的研究使用补充了β-胡萝卜素的半精制饲料，不仅未发现光保护作用，反而导致UV致癌表达显著加剧。基于β-胡萝卜素、α-生育酚（维生素E）和维生素C之间相互作用的相对电子转移速率常数，提出了一种修复β-胡萝卜素自由基阳离子的机制，β-胡萝卜素自由基阳离子是β-胡萝卜素与许多氧化物质相互作用产生的一种强氧化性自由基。理论上认为维生素C能修复类胡萝卜素自由基阳离子。由于小鼠对维生素C没有营养需求，且已知吸烟者体内该维生素水平较低，因此有人提出，在出现光保护作用的封闭式配方饲料（不含维生素C）和导致加剧作用的半精制饲料（含有维生素C）中，维生素C相对水平的差异可能是导致反应差异的原因。给无毛小鼠喂食补充了β-胡萝卜素的半精制饲料，这些饲料含有不同水平的维生素E和C（要么增加其浓度，要么降低其浓度以反映封闭式配方饲料中的水平），并使其接受UV致癌方案。增加维生素E和C的水平并不能改善β-胡萝卜素对UV致癌作用的加剧。从饲料中去除维生素C也没有效果。降低饲料中维生素E的水平会增强β-胡萝卜素对UV致癌表达的加剧作用，表明维生素E与β-胡萝卜素存在相互作用。得出的结论是，其他人早期报道的β-胡萝卜素的光保护作用，或者我们在封闭式配方饲料研究中发现的β-胡萝卜素的无损伤作用，可能取决于与其他饮食因素的相互作用，这些因素在导致UV致癌作用加剧的半精制饲料中要么不存在，要么浓度无效。这些因素可能是其他类胡萝卜素、它们 的异构体，或者一些尚未确定的植物化学物质。
