Alcohol breakdown product damages stem cells
New research in mice has shown that stem cells in bone marrow are extremely sensitive to the main breakdown product of alcohol which causes irreversible damage to their DNA. The findings help explain why people with a rare genetic condition called Fanconi anaemia (FA) suffer bone marrow failure early in their life.
Acetaldehyde is a toxic alcohol-breakdown product produced by the liver. The new research shows that damage caused by acetaldehyde is normally kept in check by two vital control mechanisms: an enzyme that mops up the toxic acetaldehyde and a group of proteins that recognise and repair damaged DNA. The researchers found that mice lacking both these protective mechanisms develop bone marrow failure due to irreversible damage to their stem cell supply. The mice showed developmental defects, a predisposition to the blood cancer leukaemia, and were susceptible to the toxic effects of alcohol.
The findings provide the first explanation of why the bone marrow fails in patients with the rare genetic condition 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 acetaldehyde, and may therefore be unusually susceptible to DNA damage. The researchers 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.