Aug. 11, 2005 Researchers at the National Institute of Standards and Technology (NIST) have developed a new chemical analysis method that has assisted researchers at the National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health, in demonstrating a potentially important chemical link between alcohol consumption and cancer. Using this novel chemical assay, they have uncovered a chain of chemical reactions that, under physiological conditions, may lead from alcohol to a known mutagen.
It has been known for years that there is a statistical relationship between excessive alcohol consumption and an increased risk of certain cancers, particularly upper gastrointestinal cancer. Alcohol itself is not a carcinogen but is metabolized in the body to form a suspected carcinogen, acetaldehyde (AA). Then the picture gets hazier. AA is known to react with 2'-deoxyguanosine (dG)--one of the chemical components of DNA--however, the main product does not appear to be mutagenic in mammals. It also is known that AA can react with DNA to produce a known mutagen (Cr-PdG. also known as alpha-methyl-gamma-hydroxy-1, N2-propano-2'-deoxyguanosine)--but only at very high concentrations of AA that would not occur in the human body.
The missing link, according to the NIAAA researchers, is a class of chemicals called polyamines that are produced in cells and believed to be involved in cell growth. Using a sensitive chemical analysis technique called liquid chromatography/isotope-dilution mass spectrometry developed at NIST, the team showed that AA reacts with polyamines to produce crotonaldehyde (CrA). This in turn reacts with dG in DNA to produce the mutagenic Cr-PdG.
An important finding was that the reactions occurred at concentrations of AA that can be found in human saliva after drinking alcohol, while concentrations of AA in gastrointestinal tissues can be even higher. The work strongly suggests that Cr-PdG plays a key role in the pathway between alcohol consumption and cancer, and that mutations in genes that encode proteins that repair Cr-PdG and its derivatives could affect individual susceptibility to cancer from alcoholic beverage consumption.
J.A. Theruvathu, P. Jaruga, R.G. Nath, M. Dizdaroglu and P.J. Brooks. "Polyamines stimulate the formation of mutagenic 1,N2-propanodeoxyguanosine adducts from acetaldehyde." Nucleic Acids Research, Vol. 33, No. 11, pp. 3513-3520 (2005).
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