![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111
3To whom correspondence should be addressed. E-mail: rob.russell{at}tufts.edu.
ß-carotene and other carotenoids have been thought to have anti-cancer activity, either because of antioxidant activity or because of their ability to be converted to vitamin A. Nevertheless, two large scale intervention studies in humans using high doses of ß-carotene found that ß-carotene supplementation resulted in more lung cancer rather than less lung cancer among smoking and asbestos exposed populations. Studies conducted in the ferret have elucidated molecular mechanisms behind this observation, in that high-dose ß-carotene and smoke exposure in these animals leads to squamous metaplasia, a pre-cancerous lesion in the lung. High dose ß-carotene in the smoke exposed animals was found to give rise to a number of transient oxidative metabolites, which include P450 enzymes that result in the destruction of retinoic acid, and diminished retinoid signaling, and enhanced cell proliferation. In addition, eccentric cleavage ß-carotene metabolites facilitate the binding of smoke derived carcinogens to DNA. In other ferret studies low dose ß-carotene smoke exposure provided mild protection against squamous metaplasia. Thus, it appears that the explanation of the apparent paradoxical effects of ß-carotene on lung cancer is related to dose. The metabolism and breakdown of natural products should be thoroughly investigated in animal models before embarking on large scale intervention trials, particularly when using unusually high doses that greatly exceed normal dietary levels.
KEY WORDS: • ß-carotene • carotenoids • vitamin A • retinoids • lung cancer • smoking
This article has been cited by other articles:
|
|
 |
|
  P. Palozza, R. Sestito, N. Picci, P. Lanza, G. Monego, and F. O. Ranelletti The sensitivity to {beta}-carotene growth-inhibitory and proapoptotic effects is regulated by caveolin-1 expression in human colon and prostate cancer cells Carcinogenesis, November 1, 2008; 29(11): 2153 - 2161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hozawa, D. R. Jacobs Jr., M. W. Steffes, M. D. Gross, L. M. Steffen, and D.-H. Lee Relationships of Circulating Carotenoid Concentrations with Several Markers of Inflammation, Oxidative Stress, and Endothelial Dysfunction: The Coronary Artery Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in Antioxidants (YALTA) Study Clin. Chem., March 1, 2007; 53(3): 447 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.J. Alija, N. Bresgen, O. Sommerburg, C.D. Langhans, W. Siems, and P.M. Eckl {beta}-Carotene breakdown products enhance genotoxic effects of oxidative stress in primary rat hepatocytes Carcinogenesis, June 1, 2006; 27(6): 1128 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hozawa, D. R. Jacobs Jr., M. W. Steffes, M. D. Gross, L. M. Steffen, and D.-H. Lee Associations of Serum Carotenoid Concentrations with the Development of Diabetes and with Insulin Concentration: Interaction with Smoking: The Coronary Artery Risk Development in Young Adults (CARDIA) Study Am. J. Epidemiol., May 15, 2006; 163(10): 929 - 937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. M. Zornoff, L. S. Matsubara, B. B. Matsubara, M. P. Okoshi, K. Okoshi, M. Dal Pai-Silva, R. F. Carvalho, A. C. Cicogna, C. R. Padovani, E. L. Novelli, et al. Beta-Carotene Supplementation Attenuates Cardiac Remodeling Induced by One-Month Tobacco-Smoke Exposure in Rats Toxicol. Sci., March 1, 2006; 90(1): 259 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Senesse, M. Touvier, E. Kesse, J. Faivre, and M.-C. Boutron-Ruault Tobacco Use and Associations of {beta}-Carotene and Vitamin Intakes with Colorectal Adenoma Risk J. Nutr., October 1, 2005; 135(10): 2468 - 2472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Touvier, E. Kesse, F. Clavel-Chapelon, and M.-C. Boutron-Ruault Dual Association of {beta}-Carotene With Risk of Tobacco-Related Cancers in a Cohort of French Women J Natl Cancer Inst, September 21, 2005; 97(18): 1338 - 1344. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. R. Paiva, R. Novo, B. B. Matsubara, L. S. Matsubara, P. S. Azevedo, M. F. Minicucci, A. O. Campana, and L. A. M. Zornoff {beta}-Carotene Attenuates the Paradoxical Effect of Tobacco Smoke on the Mortality of Rats after Experimental Myocardial Infarction J. Nutr., September 1, 2005; 135(9): 2109 - 2113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Villamor, E. Saathoff, R. J Bosch, E. Hertzmark, A. Baylin, K. Manji, G. Msamanga, D. J Hunter, and W. W Fawzi Vitamin supplementation of HIV-infected women improves postnatal child growth Am. J. Clinical Nutrition, April 1, 2005; 81(4): 880 - 888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Duffield-Lillico and C. B. Begg Reflections on the Landmark Studies of {beta}-Carotene Supplementation J Natl Cancer Inst, December 1, 2004; 96(23): 1729 - 1731. [Full Text] [PDF]
|
|
