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Cancer Biology |
The Scripps Research Institute, La Jolla, California, USA
Correspondence: David S. Goodsell, Ph.D., The Scripps Research Institute, Department of Molecular Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. Telephone: 858-784-2839; Fax: 858-784-2860; e-mail: goodsell{at}scripps.edu Web-site: http://www.scripps.edu/pub/goodsell
Received August 7, 2006; accepted for publication August 7, 2006.
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LEARNING OBJECTIVES
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Learning Objectives
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After completing this course, the reader will be able to:
Alcohol is a substance fraught with contradictions. It is a dangerously toxic solvent, yet it has been produced and consumed since the dawn of civilization. A glass of wine or a cocktail will complement any meal and smooth out the tensions of the day, but a few more drinks will inhibit reaction times, making the consumer the major threat currently on the road. A drink or two each day will reduce the risk for heart disease, a fact vividly shown in the unexpectedly low incidence of heart disease in the French in spite of a steady diet of rich foods. More heavy drinking, however, leads to myriad and widespread health problems, including cancer.
Alcohol is detoxified in the human body in two enzymatic steps (Fig. 1
). First, alcohol is oxidized to acetaldehyde by the enzyme alcohol dehydrogenase. However, acetaldehyde is even more toxic than alcohol, so it is quickly oxidized to acetate by a second enzyme, aldehyde dehydrogenase. Both of these enzymes use the cofactor nicotinamide adenine dinucleotide (NAD) to provide the oxidizing power needed for these transformations. The need for the special redox talents of NAD places an important limit on the amount of alcohol that may be detoxified. Liver cells contain a limited supply of NAD, so these enzymes can act only as fast as it is recycled. This typically limits the detoxification rate to about one drink per hourany additional alcohol stays in the circulation until the enzymes can get around to it.
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The strongest linkage of alcohol consumption with cancer is, quite expectedly, with cancers of the mouth, pharynx, larynx, and esophagus. The mechanisms of carcinogenesis are still a matter of study and debate, but two probable mechanisms involve the enzymes of alcohol detoxification. The acetaldehyde formed in the first step may be a major culprit. Acetaldehyde is a reactive compound that forms covalent complexes with proteins and DNA, and thus may act as a mutagen. Alcohol abuse also induces the production of a specific cytochrome P450 enzymeCYP2E1 (Fig. 2
)which is able to work with alcohol dehydrogenase to oxidize alcohol. This enzyme, however, also forms dangerous reactive oxygen species and can activate environmental procarcinogens into their carcinogenic forms.
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2 Fleming M, Mihic SJ, Harris RA. Ethanol. In: Goodman and Gilmans The Pharmacological Basis of Therapeutics, Eleventh Edition. New York: McGraw-Hill, 2006:591606.
3 Seitz HK, Stickel F, Homann N. Pathogenetic mechanisms of upper aerodigestive tract cancer in alcoholics. Int J Cancer 2004;108:483487.[CrossRef][Medline]
This article has been cited by other articles:
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G. A. Barclay, J. Barbour, S. Stewart, C. P. Day, and E. Gilvarry Adverse physical effects of alcohol misuse Adv. Psychiatr. Treat., March 1, 2008; 14(2): 139 - 151. [Abstract] [Full Text] [PDF] |
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