Alcohol by-product destroys blood stem cells

August 27, 2012

(Medical Xpress)—Scientists at the Medical Research Council (MRC) Laboratory of Molecular Biology have found that stem cells in the body's 'blood cell factory'—the bone marrow—are extremely sensitive to the main breakdown product of alcohol, which causes irreversible damage to their DNA.

New research in mice, published today in Nature, shows that this damage is normally kept in check by two vital : an enzyme that mops up the toxic breakdown product (acetaldehyde) and a group of proteins that recognise and repair damaged DNA. Mice lacking both these protective mechanisms develop , due to obliteration of their blood stem cells.

The findings provide the first explanation of why the bone marrow fails in patients with a called Fanconi anaemia (FA). People with this disease inherit mutations in one or more of the FA genes, which leads to inactivation of the 'repair kit' that would fix DNA damage caused by acetaldehyde. As a result, FA patients suffer from developmental defects, bone marrow failure and an extremely high risk of blood and other cancers.

If replicated in humans, the findings may also be significant for around a quarter of a billion people worldwide with alcohol-induced "Asian flush syndrome". These individuals are deficient in the enzyme (ALDH2) that removes toxic and may therefore be unusually susceptible to DNA damage. The authors believe that alcohol consumption in this population may result in permanent damage to their blood stem cells, increasing their risk of blood cancers, bone marrow failure and accelerated ageing.

Dr KJ Patel, who led the research at the MRC Laboratory of , said: "Blood stem cells are responsible for providing a continuous supply of healthy 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 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.

"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. in these individuals could overload their FA DNA repair kit causing irreversible damage to their blood . The long-term consequences of this could be bone marrow dysfunction and the emergence of ."

Sir Hugh Pelham, Director of the MRC Laboratory of Molecular Biology, said: "This study provides much sought-after explanation of the biology underpinning the devastating childhood disease Fanconi anaemia. 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."

Explore further: Excess alcohol could damage our DNA

More information: The paper, entitled 'Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function', is published in Nature. dx.doi.org/10.1038/nature11368

Related Stories

Excess alcohol could damage our DNA

July 7, 2011
Researchers from the Medical Research Council (MRC) have uncovered for the first time how excess alcohol can cause irreparable damage to our DNA. In a new study published in the journal Nature today, MRC scientists also discovered ...

Stabilizing Fanconi anemia with antioxidants

May 15, 2012
Fanconi anemia (FA) is a rare genetic disorder which affects one person in 350,000. People affected by this disease have defects in DNA repair, and are hypersensitive to oxidative damage, resulting in bone marrow failure ...

Alcohol metabolism causes DNA damage and triggers a breast cancer-related DNA damage response

September 15, 2011
Alcohol is known to be carcinogenic to humans in the upper aerodigestive tract, liver, colorectum, and the female breast. Evidence suggests that acetaldehyde, the primary metabolite of alcohol, plays a major role in alcohol-related ...

Recommended for you

Researchers find way to convert bad body fat into good fat

September 19, 2017
There's good fat and bad fat in our bodies. The good fat helps burn calories, while the bad fat hoards calories, contributing to weight gain and obesity. Now, new research at Washington University School of Medicine in St. ...

New model may help science overcome the brain's fortress-like barrier

September 19, 2017
Scientists have helped provide a way to better understand how to enable drugs to enter the brain and how cancer cells make it past the blood brain barrier.

Cell-based therapy success could be boosted by new antioxidant

September 19, 2017
Cell therapies being developed to treat a range of conditions could be improved by a chemical compound that aids their survival, research suggests.

Study suggests epilepsy drug can be used to treat form of dwarfism

September 19, 2017
A drug used to treat conditions such as epilepsy has been shown in lab tests at The University of Manchester to significantly improve bone growth impaired by a form of dwarfism.

Research predicts how patients are likely to respond to DNA drugs

September 19, 2017
Research carried out by academics at Northumbria University, Newcastle could lead to improvements in treating patients with diseases caused by mutations in genes, such as cancer, cystic fibrosis and potentially up to 6,000 ...

Urine output to disease: Study sheds light on the importance of hormone quality control

September 18, 2017
The discovery of a puddle of mouse urine seems like a strange scientific "eureka" moment.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.