Researchers at the National Institute of Standards and Technology(NIST) have developed a new chemical analysis method that has assistedresearchers at the National Institute of Alcohol Abuse and Alcoholism(NIAAA), National Institutes of Health, in demonstrating a potentiallyimportant chemical link between alcohol consumption and cancer. Usingthis novel chemical assay, they have uncovered a chain of chemicalreactions that, under physiological conditions, may lead from alcoholto a known mutagen.
It has been known for years that there is a statistical relationshipbetween excessive alcohol consumption and an increased risk of certaincancers, particularly upper gastrointestinal cancer. Alcohol itself isnot a carcinogen but is metabolized in the body to form a suspectedcarcinogen, acetaldehyde (AA). Then the picture gets hazier. AA isknown to react with 2'-deoxyguanosine (dG)--one of the chemicalcomponents of DNA--however, the main product does not appear to bemutagenic in mammals. It also is known that AA can react with DNA toproduce a known mutagen (Cr-PdG. also known asalpha-methyl-gamma-hydroxy-1, N2-propano-2'-deoxyguanosine)--but onlyat very high concentrations of AA that would not occur in the humanbody.
The missing link, according to the NIAAA researchers, is a class ofchemicals called polyamines that are produced in cells and believed tobe involved in cell growth. Using a sensitive chemical analysistechnique called liquid chromatography/isotope-dilution massspectrometry developed at NIST, the team showed that AA reacts withpolyamines to produce crotonaldehyde (CrA). This in turn reacts with dGin DNA to produce the mutagenic Cr-PdG.
An important finding was that the reactions occurred at concentrationsof AA that can be found in human saliva after drinking alcohol, whileconcentrations of AA in gastrointestinal tissues can be even higher.The work strongly suggests that Cr-PdG plays a key role in the pathwaybetween alcohol consumption and cancer, and that mutations in genesthat encode proteins that repair Cr-PdG and its derivatives couldaffect individual susceptibility to cancer from alcoholic beverageconsumption.
J.A. Theruvathu, P. Jaruga,R.G. Nath, M. Dizdaroglu and P.J. Brooks. "Polyamines stimulate theformation of mutagenic 1,N2-propanodeoxyguanosine adducts fromacetaldehyde." Nucleic Acids Research, Vol. 33, No. 11, pp. 3513-3520(2005).
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