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How Binge Drinking Causes Fetal Damage

Studies in mice show that alcohol is toxic to DNA in the absence of two specialized enzymes.


Mutations in fetal DNA.
Photo via medicineworld

By Dirk Hanson


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We know pregnant women shouldn’t drink. But some women do. It can cause permanent damage to the unborn child, including Fetal Alcohol Spectrum Disorder, better known as Fetal Alcohol Disorder (FAS). But the precise mechanisms by which alcohol can manage to disrupt the normal development of a fetus are not well understood. A new article in Nature detailed
 the discovery of one way alcohol causes irreparable damage to fetal DNA. Scientists with the UK’s Medical Research Council used genetically-modified mice to show that alcohol’s primary breakdown product, acetaldehyde, is toxic to cellular DNA in the absence of two specialized enzymes. The first set of enzymes removes excess acetaldehyde as it builds up, and the second enzymatic mechanism kicks in if a flood of acetaldehyde causes damage to cellular DNA. These latter enzymes, known as the Fanconi proteins, are literally a life-and-death barrier that keeps alcohol from causing widespread genetic damage. “The findings show how critically reliant we are on both these control systems to prevent alcohol from causing irreversible mutations to DNA, both in the fetus and in our own cells,” said lead researcher Ketan Patel at the Medical Research Council’s Laboratory of Molecular Biology in Cambridge. Pregnant lab mice lacking both protective enzyme mechanisms showed major fetal damage, including destruction of blood stem cells, after the equivalent of a single episode of binge drinking, Patel said. “The effects of alcohol in the modified pregnant mice resembled fetal alcohol syndrome,” he said. “With alcohol you are essentially drinking a mutagen.”

These findings dovetail with  the condition known in Asia as the alcohol flushing mutation. Millions of Chinese in others in Southeast Asia have this inherited condition, which causes an inability to rapidly break down and excrete acetaldehyde. One symptom of this is the flush reaction. One piece of unsettling speculation based on the new findings is that those who suffer from the Asian flush reaction may be more susceptible to DNA damage. Dr. Hugh Pelham, director of MRC’s Laboratory of Molecular Biology, took the opportunity to bestow laurels on his scientists, noting that they had shown “how vulnerable we can be to DNA damage from excess alcohol and even more so in the womb. Despite the existence of protective mechanisms, long-term genetic damage must be added to the risks of excessive alcohol consumption.”

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