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Drinking alcohol has been correlated to various cancers. Now, scientists have pinpointed a possible causal link in the way cells react to alcohol.
It is known, from many statistical studies, that consuming alcoholic beverages is associated to several types of cancer, including breast and colorectal cancer. But up till now, just how this happened at the biological level was not understood.
A team in the UK has identified a probable cause for this association in hematopoietic stem cells: DNA damage induced by a byproduct of ethanol (another name for drinking alcohol) on these stem cells. The research has been published in the journal Nature.
Stem cells are cells that are able to give rise to all body tissues, and are still produced in adult life. In particular, hematopoietic stem cells give rise to white and red blood cells.
One of the novelties of this work is that, instead of trying to determine what alcohol does to cells in a petri dish, Ketan Patel, from the Medical Research Council’s Laboratory of Molecular Biology in Cambridge, and his colleagues, performed their experiments on living animals.
They gave diluted ethanol to mice and studied the effect on the animals’ hematopoietic stem cells. When healthy stem cells (and not only blood stem cells) become dysfunctional, they can give rise to cancer.
“Some cancers develop due to DNA damage in stem cells”, says Patel in a statement issued by the charity Cancer Research UK, that in part funded the project. So the scientists wanted to see if this could be due to DNA alterations caused by alcohol to these cells.
To test this, the team analysed the chromosomes and sequenced the DNA of blood stem cells to determine whether one of its byproducts, acetaldehyde, could be a culprit for DNA damage. Acetaldehyde is a harmful chemical produced when the body metabolizes alcohol.
What they discovered was that acetaldehyde can actually damage chromosomes and cause mutations in the DNA of blood stem cells in a profound and permanent way. “While some damage occurs by chance”, Patel says, “our findings suggest that drinking alcohol can increase the risk of this damage.”
The body has ways to cope with acetaldehyde and protect itself – in particular thanks to a class of enzymes that break down acetaldehyde into a potentially beneficial compound. But millions of people in the world, in particular in South East Asia, lack these enzymes or have defective versions of them. For those individuals, the risk of drinking alcohol could be greater.
To show this, the scientists did a further experiment: they gave diluted ethanol to mutant mice lacking a critical such enzyme, called aldehyde dehydrogenase 2 (ALDH2). And the result was that these animals presented four times more DNA damage in their blood stem cells than non-mutant mice.
There are also mechanisms for repairing the DNA damage when the first, aldehyde-clearing line of defence mounted by ALDHs fails. However, as Patel warns in an article he authored in the site theconversation.com, even when intact, these defence mechanisms are not perfect and do not completely protect the body against alcohol-related cancers.
The results could also apply to other types of stem cells, but this possibility has yet to be studied. In any case, “the analysis of blood stem cells provides a window into how alcohol may damage other stem cells in the body, such as those that make the gut and the liver”, Patel writes.
Ana Gerschenfeld works as a Science Writer at the Science Communication Office at the Champalimaud Neuroscience Programme
Edited by: Catarina Ramos(Science Communication office). Photo credit: Nogas1974(Creative Commons CC BY-SA 4.0)