Drinking alcoholic beverages has been linked to an increased risk ofupper gastrointestinal cancer and other types of cancer. Researcherslooking for the potential biochemical basis for this link have focusedon acetaldehyde, a suspected carcinogen formed as the body metabolizesalcohol. In the journal Nucleic Acids Research, scientists from theNational Institute on Alcohol Abuse and Alcoholism (NIAAA) and theNational Institute of Standards and Technology (NIST) report thatpolyamines -- natural compounds essential for cell growth -- react withacetaldehyde to trigger a series of reactions that damage DNA, an eventthat can lead to the formation of cancer.
"We've long suspected acetaldehyde's role in the carcinogenicity ofalcohol beverage consumption, but this study gives us important newclues about its involvement," says Ting-Kai Li, M.D., director of theNIAAA, part of the National Institutes of Health. "This work providesan important framework for understanding the underlying chemicalpathway that could explain the association between drinking and certaintypes of cancer."
The research team, led by P.J. Brooks, Ph.D., of NIAAA andMiral Dizdaroglu, Ph.D., of NIST, examined acetaldehyde's reaction withpolyamines, small molecules found in all cells. "Polyamines are usuallyconsidered 'good guys,' because they have been shown to protect DNAfrom oxidative damage," says Dr. Brooks. Yet the researchers found thepolyamines facilitated the conversion of acetaldehyde intocrotonaldehyde (CrA), an environmental pollutant that has been shown tocause cancer in animals. This chemical in turn altered DNA, generatingan abnormal, mutagenic DNA base called a Cr-PdG adduct. Dr. Brookssays, "We concluded that polyamines stimulated the formation of Cr-PdGadducts from acetaldehyde, and this may provide a mechanism to explainhow alcohol consumption increases the risk of some types of cancer."
Previous studies had shown acetaldehyde could be converted tomutagenic Cr-PdG, but those studies used very high acetaldehydeconcentrations. "We were able to demonstrate that these reactions cantake place with acetaldehyde concentrations that have been measured inhuman saliva during alcohol consumption," says Dr. Brooks.
An important part of this research was a new chemical analysismethod developed at NIST. According to Dr. Dizdaroglu, "This novelchemical assay is a powerful method that accurately measures the Cr-PdGadduct."
George Kunos, M.D., Ph.D., director of NIAAA's Division ofIntramural Clinical and Biological Research, says, "These findings alsohave significant implications for researchers seeking to understand howgenes affect the risk for cancer." Many studies have shown that certaingenetic variants that affect alcohol and acetaldehyde metabolism canalso affect individual susceptibility to alcohol-relatedgastrointestinal cancer. Dr. Kunos adds, "This work could serve as aroadmap for future studies to investigate other genetic factors,particularly those that influence DNA repair pathways, in relation toalcohol consumption and cancer."
The National Institute on Alcohol Abuse and Alcoholism, a component ofthe National Institutes of Health, U.S. Department of Health and HumanServices, conducts and supports approximately 90 percent of U.S.research on the causes, consequences, prevention, and treatment ofalcohol abuse, alcoholism, and alcohol problems and disseminatesresearch findings to science, practitioner, policy making and generalaudiences. Additional alcohol research information and publications areavailable at www.niaaa.nih.gov.
Materials provided by NIH/National Institute on Alcohol Abuse and Alcoholism. Note: Content may be edited for style and length.
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