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There's Now "Very Strong Evidence" That Alcohol Can Directly Damage DNA

Well, crap. 

MICHELLE STARR
4 JAN 2018
 

There is an increasing body of evidence linking alcohol consumption to an increased cancer risk - and now scientists in the UK believe they have found a plausible explanation.

 

In a new mouse study, the team found that alcohol damages DNA in blood-forming stem cells.

The culprit is a chemical compound called acetaldehyde, a byproduct of the alcohol metabolisation process.

When acetaldehyde isn't broken down further - for instance, when one has consumed alcohol in amounts that the body struggles to metabolise - it builds up in the cells.

This is when it wreaks its merry havoc on DNA, according to researchers from Cambridge University's MRC Laboratory of Molecular Biology.

"How exactly alcohol causes damage to us is controversial," lead author Ketan Patel told The Guardian.

"This paper provides very strong evidence that an alcohol metabolite causes DNA damage [including] to the all-important stem cells that go on to make tissues."

Previous research found that acetaldehyde causes damage to DNA, but these experiments were conducted on cells in a dish, not in a living body.

By using a living organism, scientists can observe the way a body responds - so this mouse study was a critical advancement in understanding what is going on.

They gave the mice diluted alcohol, or ethanol, then used chromosome analysis and DNA sequencing to gauge the genetic damage. They found that acetaldehyde can damage and cause double-stranded breaks in the DNA inside these cells, permanently altering it.

 

Blood stem cells were used because they can be easily replicated for DNA analysis, but also because stem cells could be spreading their genetic damage throughout the body.

The body does have a defence against acetaldehyde - a group of enzymes called acetaldehyde dehydrogenases (ALDH). When these are working properly, they neutralise acetaldehyde by converting it into acetate, which the body can use for energy.

In order to see how acetaldehyde affects cells when it builds up, the team had to genetically modify mice with a mutation that prevented blood stem cells from producing one of these enzymes, ALDH2.

"We saw huge amounts of DNA damage in these cells. Bits of DNA were deleted, bits were broken and we even saw parts of chromosomes being moved about and rearranged," Patel said.

The ALDH2-deficient mice had four times the cell damage as control mice with normal ALDH2 production.

The second defence is a repair system, where the body will get to work trying to fix the damage done to the DNA. But some people have mutations where one or both of these defences don't work.

 

For instance, around 540 million people in Asia carry a mutation in the ALDH2 gene, which means they can't process acetaldehyde (one of the factors in the red flush reaction). People with this mutation are at an increased risk of oesophageal cancer, the researchers said.

Other people have faults in the molecules that conduct the DNA repairs, which means their body will try to use other mechanisms.

"Our study highlights that not being able to process alcohol effectively can lead to an even higher risk of alcohol-related DNA damage and therefore certain cancers," Patel said.

"But it's important to remember that alcohol clearance and DNA repair systems are not perfect and alcohol can still cause cancer in different ways, even in people whose defence mechanisms are intact."

Next, the team intends to study why alcohol consumption is linked to some cancers and not others.

Previous research doesn't paint a pretty picture, finding associations with an increased risk of mouth, throat, oesophageal, larynx, breast, liver and bowel cancer, even for light drinking, with increased mortality.

The team's research has been published in the journal Nature.

 

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