Modulation of Dietary Vitamins E and C Fails to Ameliorate β-Carotene Exacerbation of UV Carcinogenesis in Mice

β-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 β-carotene, when added to commercial closed-formula rodent diets, provided significant photoprotection to ultraviolet light (UV) carcinogenesis. However, clinical trials found that β-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 β-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 β-carotene, a-tocopherol (vitamin E), and vitamin C, a mechanism was proposed for the repair of β-carotene radical cation, a strongly oxidizing radical resulting from β-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 β-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 β-carotene exacerbation of UV carcinogenesis. Nor did elimination of vitamin C from the diet. Reduced levels of dietary vitamin E augmented β-carotene exacerbation of UV carcinogenic expression, suggesting vitamin E and β-carotene interaction. It is concluded that the photoprotective effect of β-carotene reported earlier by others, or the noninjurious effect of β-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).