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New research shows how alcohol damages DNA, which may increase cancer risk (2018-01-29)

Scientists have shown how alcohol damages DNA in stem cells, which may help to explain how drinking alcohol is linked to an increased risk of cancer, according to research led by scientists from the MRC Laboratory of Molecular Biology and part-funded by Cancer Research UK.

Scrambled chromosomes after exposure of mice to ethanol. Credit: J. Garaycoechea, MRC LMB

Much previous research looking at the precise ways in which alcohol causes cancer has been done in cell cultures.

But in this study, published in Nature researchers used mice to show how alcohol exposure leads to permanent genetic damage.

The scientists gave diluted alcohol, chemically known as ethanol, to mice.

They then used chromosome analysis and DNA sequencing to examine the genetic damage caused by acetaldehyde, a harmful chemical produced when the body processes alcohol.

They found that acetaldehyde can break and damage DNA within blood stem cells leading to rearranged chromosomes and permanently altering the DNA sequences within these cells.

It is important to understand how the DNA blueprint within stem cells is damaged, because when healthy stem cells become faulty they can give rise to cancer.

Professor Ketan Patel lead author of the study and scientist, part-funded by Cancer Research UK, at the MRC Laboratory of Molecular Biology, said: “Some cancers develop due to DNA damage in stem cells.
While some damage occurs by chance, our findings suggest that drinking alcohol can increase the risk of this damage.”

The study also examined how the body tries to protect itself against damage caused by alcohol.

The first line of defence is a family of enzymes called aldehyde dehydrogenases (ALDH).

These enzymes break down harmful acetaldehyde into acetate, which our cells can use as a source of energy.

Worldwide, millions of people, particularly those from South East Asia, either lack these enzymes or carry faulty versions of them.

So, when they drink, acetaldehyde builds up which causes a flushed complexion, and also leads to them feeling unwell.

In the study, when mice lacking the critical ALDH enzyme - ALDH2 - were given alcohol, it resulted in four times as much DNA damage in their cells compared to mice with the fully functioning ALDH2 enzyme.

The second line of defence used by cells is a variety of DNA repair systems which, most of the time, allow them to fix and reverse different types of DNA damage.

But they do not always work and some people carry mutations which mean their cells are not able to carry out these repairs effectively.

Professor Patel added: “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.

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.”

The study tested blood stem cells because properties of these cells enabled the scientists to demonstrate how the DNA within individual cells was damaged.

They did this by grafting single blood stem cells from mice exposed to alcohol into recipient mice, where the cells multiplied and could then be submitted to whole genome sequencing.

This research was funded by Cancer Research UK, Wellcome and the MRC.

For more information
Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells

Source: UK Medical Research Council