Alcohol abuse is bad for your health, it’s a fact. And the links between ethanol-containing beverages and cancer are tightening. In a new study conducted on mice now published in the journal Nature, a British research team found that alcohol damages the DNA of hematopoietic stem cells. The culprit is a chemical compound called acetaldehyde, a byproduct of the process of metabolizing alcohol.
The study indicates that alcohol consumption leads to genetic mutations of stem cells and irreversible damage to DNA. It also shows that by modifying the DNA molecules of stem cells, the consumption of alcohol would result in the development of certain cancers. When the body can no longer break down acetaldehyde, for example when alcohol has been consumed in amounts that the body has difficulty metabolizing, it accumulates in the cells.
“How exactly alcohol causes damage to us is controversial,” said Prof Ketan Patel, who led the work at the MRC Laboratory of Molecular Biology in Cambridge, to 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.”
The researchers gave the mice diluted alcohol, or ethanol, and then used chromosome analysis and DNA sequencing to assess the genetic damage. They found that acetaldehyde can damage and cause double-strand breaks in the DNA inside these cells by permanently altering it. The scientists used blood stem cells for the study because they can easily be replicated for DNA analysis, but also because they can also spread their genetic damage throughout the body.
“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 defense mechanisms are intact,” Professor Ketan Patel explained. “Actually the blood system has a very stringent quality control mechanism to get rid of anything that is damaged,” he added.
The body does have a defense system against acetaldehyde: a group of enzymes called acetaldehyde dehydrogenases (ALDH). When these work properly, they neutralize acetaldehyde by converting it to acetate, which the body can then use to generate energy.
In order to see how acetaldehyde affects cells as they accumulate in the body, the team had to genetically engineer the mice to have a mutation that prevents blood stem cells from producing any of these enzymes, ALDH2. “We have seen huge amounts of DNA damage in these cells. DNA pieces were removed, pieces were broken and we even saw parts of chromosomes displaced and rearranged, “said Patel.
Mice deficient in ALDH2 had four times more cell damage than mice in the control group with normal production of ALDH2. The second defense is a so-called repair system, where the body will try to repair DNA damage itself. But some people have mutations, so one or the other defenses do not work.
For example, about 540 million people in Asia have a mutation in the ALDH2 gene, which means that they can not treat acetaldehyde. In addition, people with this mutation are at increased risk of esophageal cancer, the researchers said. Other people have defects in the molecules that perform the DNA repairs, which means that their bodies will try to use other mechanisms.
Previous research had already revealed that acetaldehyde causes damage to DNA, but these experiments were conducted on cells in a sample, not in a living body. By using a living organism, scientists can observe how a body reacts: this mouse study is therefore a crucial step forward in understanding what is really happening in such circumstances.
“This research highlights the damage that alcohol can cause to our cells, which is more serious than a simple hangover,” says Professor Linda Bauld, a British cancer prevention expert.