Carcinogenic Carotene

Carotenoid oxidation products are also supposed to have detrimental effects in vivo. As mentioned earlier, they are suspected to be involved in the adverse effects of high doses of 3-carotene supplementation in smokers and asbestos workers (CARET and ATBC studies) and in smoke-exposed ferrets. The mechanisms potentially involved have been investigated in vitro. P-Apo-8 -carotenal, an eccennic cleavage oxidation product of P-carotene, was shown to be a strong inducer of CYPlAl in rats, whereas P-carotene was not active. Cytochrome P450 (CYP 450) enzymes thus induced could enhance the activation of carcinogens and the destruction of retinoic acid. ... 

Lisle, E.B., The effect of carcinogenic and other related compounds on the autoxidation of carotene and other autoxidizable systems. Cancer Res., 11, 153, 1951. 

Paolini, M., Cantelli-Forti, G., Perocco, P., Peduli, G.F., Abdel-Rahman, S.Z., and Legator, M.S. 1999. Co-carcinogenic effect of beta-carotene. Nature 398 760-761. 

Perocco, P., Paolini, M. Mazzullo, M. Biagi, GL., and Cantelli-Forti, G. 1999. Beta-carotene as enhancer of cell transforming activity of powerful carcinogens and cigarette-smoke condensate on BALB/c 3T3 cells in vitro. Mutat Res 440 83-90. 

Edes, T. E., Gysbers, D. G., Buckley, C. S., and Thornton, W. H., Jr. (1991). Exposure to the carcinogen benzopyrene depletes tissue vitamin A Beta-carotene prevents depletion. 

Mutagenesis induced in Salmonella typhimurium by 2-fluorenamine and other chemical carcinogens was inhibited by low levels of retinol and other retinoids when carcinogen activation was carried out by rat liver microsomes. In contrast, low levels of retinoids enhanced mutagenesis when carcinogen activation was mediated by whole liver homogenates. There was no effect of the provitamin 3-carotene in this test system. 

In no instance did the synthetic retinoid possess as great an inhibitory capacity as do retinol or retinyl acetate. In addition, the provitamin g-carotene had no effect on mutagenicity of 2-fluorenamine in Salmonella regardless of the carcinogen activation system (Tables III and IV). Thus, 3-carotene would apparently require enzymatic cleavage to vitamin A in order to have an effect in this ijri vitro bioassay and exerts no role by itself in modulating the metabolism of chemical carcinogens in the model system. 

Modulation of Mutagenicity by the Intestinal Carcinogen 3,21-Dimethyl-4-Aminobiphenyl. We wished to examine the effect of retinol, 3-carotene and 13-cis-retinoic acid on yet another aromatic amine,... 

Cows eat fresh, green grass that contains carotene, but they do not metabolize the carotene entirely, and so it ends up in their milk. Butter made from this milk is therefore yellow. In the winter the silage cows eat does not contain carotene because it readily undergoes air oxidation, and the butter made at that time is white. For some time an azo dye called Butter Yellow was added to winter butter to give it the accustomed color, but the dye was found to be a carcinogen. Now winter butter is colored with synthetic carotene, as is all margarine. 

Negative outcomes in several supplementation trials of beta-carotene, especially the results of the Finnish Alpha-Tocopherol Beta-Carotene (ATBC) Cancer Prevention Study (63) (SEDA-20, 363), have again revived discussion about the carcinogenic potential of beta-carotene. The ATBC trial showed that there was a statistically significant increase in the incidence of lung cancer in heavy smokers who took beta-carotene. 

The carcinogenic effect of beta-carotene has recently been found to be reduced by vitamin E (74), suggesting that, rather than individual micronutrient supplementation, combinations of various such substances might be more advantageous. 

Besides its hepatotoxic effects, beta-carotene supplementation can also cause cardiovascular complications in smokers and potentiate carcinogenicity. The Alpha-Tocopherol, Beta-Carotene and Cancer Prevention Study (ATBC) (72) and CARET (99) showed that supplementation of beta-carotene in smokers increased the incidence of death from coronary artery disease. Recent results suggest that beta-carotene participates as a prooxidant in the oxidative degradation of LDL, and that raised LDL concentrations may cancel the protective effect of alpha-tocopherol (102). 

Wang XD, Russell RM. Procarcinogenic and anti-carcinogenic effects of beta-carotene. Nutr Rev 1999 57(9 Pt l) 263-72. 

Leo MA, Lieber CS. Alcohol, vitamin A, and beta-carotene adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr 1999 69(6) 1071-85. 

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