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Department of Food Science and Technology Cornell University Geneva, NY 14456 E-mail: cyl1{at}cornell.edu
Dear Sir:
In recent letters to the Journal by Horrobin (1) and Zeisel (2), the unexpected failure of ß-carotene in clinical trials of lung cancer (3) was explained by the fact that free radicals may be involved both in the elimination of cancer cells and in the generation of mutations that help to initiate cancer. Although the cancer-preventive effects of ß-carotene appear to originate mainly in its strong free radical scavenging activity against DNA damage, ß-carotene has also been shown to modulate cell proliferation and differentiation through antiproliferative effects on human lung cancer cells (4) and through the enhancement of gap junctional intercellular communication (5). When these effects are taken into account, ß-carotene does not appear to promote lung cancer by free radical elimination.
Recently, it was reported that, despite its possible procarcinogenic action as indicated in an editorial by van der Vliet (6), ß-carotene acts as an antitumor promoter rather than as a tumor promoter in a 2-stage model of skin carcinogenesis (7). We speculate that the reason for ß-carotene's failure in the lung cancer trials can be explained by multistage carcinogenesis. Most of the elderly persons with long-term smoking habits who participated in the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study (3) were likely to have mutated genes or premalignant lesions before starting the ß-carotene supplementation. Because ß-carotene is believed to be most effective in the initiation and promotion stages of carcinogenesis, it may not have shown beneficial effects in the progression stage. Therefore, we believe that ß-carotene does not promote cancer.
However, we do not recommend ß-carotene as a dietary supplement to prevent cancer, either. A recent study showed an inverse relation between plasma vitamin C and mortality due to cancer (8). Similar results of lower cancer mortality were obtained in another study that examined daily fruit consumption (9). Recently, we reported that most of the antioxidant and antiproliferative activities of apples result not from vitamin C but mainly from the synergistic effects of phytochemicals (nonvitamins) (10). These results suggest that the cancer-preventive effects of vegetables and fruit may result from phytochemicals rather than from ß-carotene, vitamin C, and vitamin E. Therefore, we suggest that balanced diets high in phytochemicals and vitamins may be more advantageous than dietary supplements of single vitamins alone.
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