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Alcohol Permanently Damages Blood Stem Cells

Update Date: Aug 28, 2012 08:01 AM EDT

A new study by researchers from the Medical Research Council (MRC) Laboratory of Molecular Biology claims that stem cells in the body's 'blood cell factory' -the bone marrow - are extremely sensitive to the main byproduct of alcohol, which causes a permanent damage to their DNA.

The research conducted on mice reveals that usually, this damage is kept in control by two mechanisms: an enzyme that wipes out the toxic breakdown product (acetaldehyde) and a group of proteins that recognize and repair damaged DNA.

Mice that lacked both these protective mechanisms apparently developed bone marrow failure, due to damaged blood stem cells.

This is the first time a study has been able to explain why bone marrow failure occurs in patients with a rare genetic condition called Fanconi anemia (FA).

According to the report, this disease apparently inactivates the "repair kit", due to certain mutations in one or more of the FA genes, and hence the DNA damage caused by acetaldehyde remains unfixed.

This in turn results in developmental defects and bone marrow failure in FA patients, also making them highly prone to blood and other cancers.

In humans, these findings may be significant for around a quarter of a billion people around the world with alcohol-induced "Asian flush syndrome". These individuals, deficient in the enzyme ALDH2 may be unusually at risk of DNA damage. According to the authors of the study, this population could see a permanent DNA damage with alcohol consumption, making them highly prone to blood cancers, bone marrow failure and accelerated aging, Medical Xpress reported.

"Blood stem cells are responsible for providing a continuous supply of healthy blood cells throughout our lifespan. With age, these vital stem cells become less effective because of the build up of damaged DNA. Our study identifies a key source of this DNA damage and defines two protective mechanisms that stem cells use to counteract this threat. Last year we published a paper showing that without this two-tier protection, alcohol breakdown products are extremely toxic to the blood. We now identify exactly where this DNA damage is occurring, which is important because it means that alcohol doesn't just kill off healthy circulating cells, it gradually destroys the blood cell factory. Once these blood stem cells are damaged they may give rise to leukaemias and when they are gone they cannot be replaced, resulting in bone marrow failure," Dr KJ Patel, who led the research at the MRC Laboratory of Molecular Biology, said.

"The findings may be particularly significant for a vast number of people from Asian countries such as China, where up to a third of the population are deficient in the ALDH2 enzyme. Alcohol consumption in these individuals could overload their FA DNA repair kit causing irreversible damage to their blood stem cells. The long-term consequences of this could be bone marrow dysfunction and the emergence of blood cancers," Patel added.

"This study provides much sought-after explanation of the biology underpinning the devastating childhood disease Fanconi anemia. In future this work may underpin new treatments for this genetic disease, which currently is associated with a very poor prognosis. It also helps to inform large numbers of the global population, who are deficient in the ALDH2 enzyme, that drinking alcohol may be inflicting invisible damage on their DNA," Sir Hugh Pelham, director of the MRC Laboratory of Molecular Biology, said.

The study was published Tuesday in the journal Nature.

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