How alcohol damages DNA and increases cancer risk

Scientists have shown how alcohol damages DNA in stem cells, helping to explain why drinking increases your risk of cancer, according to research part-funded by Cancer Research UK and published in Nature today (Wednesday).

Much previous research looking at the precise ways in which alcohol causes cancer has been done in cell cultures. But in this study, researchers have used mice to show how alcohol exposure leads to permanent genetic damage.

Scientists at the MRC Laboratory of Molecular Biology, Cambridge, 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.

These new findings therefore help us to understand how drinking alcohol increases the risk of developing 7 types of cancer including common types like breast and bowel.

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 don't always work and some people carry mutations which mean their cells aren't 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."

This research was funded by Cancer Research UK, Wellcome and the Medical Research Council (MRC).

Professor Linda Bauld, Cancer Research UK's expert on cancer prevention, said: "This thought-provoking research highlights the damage alcohol can do to our cells, costing some people more than just a hangover.

"We know that alcohol contributes to over 12,000 cancer cases in the UK each year, so it's a good idea to think about cutting down on the amount you drink."

'Vaccine Against HIV Closer To Reality', Say Researchers

Melbourne: In a significant progress towards the development of a vaccine against HIV, scientists have developed a new approach to help the immune system actively fight the virus in the body.

For the first time, researchers showed that a combined approach - using a common cold virus to introduce a vaccine into the body, as well as an injection of a DNA-based vaccine - may help protect against HIV in the gut and bodily cavities.

"With sexual activity being one of the primary methods of HIV transmission, it is necessary to try to protect those parts of the body that are most likely to encounter the virus first," said Branka Grubor-Bauk, from the University of Adelaide in Australia.

"A possible reason why previous HIV vaccine trials have not been successful is because of this lack of a front-line protection," Mr Grubor-Bauk said.

The laboratory studies, conducted so far in mice represent an important step forward in attempts to introduce a first line of defence against HIV at the site of infection.

"In mice, we delivered a rhinovirus (or common cold virus) inside the nose, and this virus had been altered to include HIV proteins," Mr Grubor-Bauk said.

"At the same time, the mice also received an injection into the skin containing a DNA-based vaccine. This approach resulted in very specific responses in the immune system," she said.

"This vaccine approach encompasses two different arms of the immune system: white blood cells that attack the HIV virus, and specific antibodies that recognise and shut down HIV-positive cells," she added.

"There is an element of HIV known as Tat that helps the virus to replicate quite rapidly," said Eric Gowans, professor at University of Adelaide.

The antibodies inhibit the Tat effect, preventing HIV from replicating itself, Mr Gowans added.

"Overall, we found that infection was considerably reduced in the mice we studied," he said.

The study appears in the journal Scientific Reports.

Zika vaccine to begin human testing

WASHINGTON (AP): An experimental vaccine for the Zika virus is due to begin human testing in coming weeks, after getting the green light from United States health officials.

Inovio Pharmaceuticals yesterday said it received clearance from the Food and Drug Administration to begin early-stage safety tests of its DNA-based vaccine against the mosquito-borne virus. That puts the company ahead of researchers at the National Institutes of Health (NIH), who have said they expect to begin testing their own DNA-based Zika vaccine by early fall.

Inovio's vaccine is intended to prime the immune system to fight Zika by introducing genetically-engineered material that mimics the virus. Inovio reports that animals tested with the vaccine developed antibodies and immune-system cells that attack Zika.

The NIH is working to develop a Zika vaccine by swapping out the genetic material from its experimental West Nile virus vaccine.

Inovio and its partner, GeneOne Life Science, plan to begin a 40-person study to determine the safest dose of the vaccine in coming weeks. Company officials said they expect results from the vaccine study by the end of 2016.

NO LICENCED DRUGS

There are currently no licensed drugs or vaccines for Zika.

Zika is spread mainly through the bite of a tropical mosquito, Aedes aegypti. It causes only a mild and brief illness, at worst, in most people. But it can cause fetal deaths and severe birth defects in the children of women infected during pregnancy.

Zika has become epidemic in Latin America and the Caribbean since last fall. Officials aren't expecting big outbreaks in the continental US, but some cases are likely as temperatures rise and mosquitoes spread.

Zika vaccine 'within months'

A Zika vaccine could be ready for human trials later this year, according to the man in charge of the US government's research programme.

Our first sex with Neanderthals happened 100,000 years ago

It was a two-way street. Many people carry ancient Neanderthal DNA in their genome as a result of cross-species liaisons around 50,000 years ago. Now it seems that some Neanderthals carried our DNA, too.

This particular group had, for example, a big chunk of modern human DNA right in the middle of a gene that may have a role in language development, called FOXP2. What’s more, they got that DNA from us at least 100,000 years ago, somewhere in Eurasia. The finding challenges an idea central to our thinking about human evolution: that our species didn’t properly leave Africa until about 60,000 years ago.

A team led by Sergi Castellano at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, compared 50,000-year-old DNA from four extinct human relatives: a Neanderthal and a Denisovan from Siberia, and two European Neanderthals. They also looked at 500 genomes from living Africans.

Neanderthals and Denisovans are more closely related to each other than they are to us, so their genomes should have more in common, too. But Castellano’s team found that parts of the Siberian Neanderthal genome were more similar to the genomes of modern-day Africans than those of the Denisovans or the European Neanderthals. Statistical analyses ruled out the possibility that those similarities were the result of contamination.

“One chunk of modern DNA found in Neanderthals was inside a gene linked to language development”

The length of the modern-day DNA segments allowed the team to estimate when they entered the Siberian Neanderthal gene pool. Recently added DNA typically exists in long segments that become shorter down the generations. The team concluded that modern humans must have first interbred with Neanderthals at least 100,000 years ago (Nature, DOI: 10.1038/nature16544).

The researchers speculate that this might have happened in the Arabian peninsula or eastern Mediterranean, based on tentative archaeological evidence that modern humans were living in those regions by then. It could also have happened further east – especially in light of the discovery last year of 47 modern human teeth in sediments in south-east China, dated to between 80,000 and 120,000 years old.

 

For many years, hypotheses that significant out-of-Africa migration could have happened that early were considered heretical, says archaeologist Michael Petraglia at the University of Oxford. The idea isn’t so outlandish any more, it seems. “This study is an eye-opener,” says María MartinÓn-Torres at University College London, who was involved in the Chinese finds. “A whole unknown episode is open now to investigate.”

Some researchers were sceptical that modern humans had reached China so early, says MartinÓn-Torres. She thinks the new DNA evidence will help convince them. Chris Stringer at London’s Natural History Museum agrees. “The search is now on for further traces of these mysterious early moderns, and their Neanderthal relatives in Asia,” he says.

It’s possible that Neanderthal DNA affects the health of modern humans (see “Should we fear our inner Neanderthal?“). Might Neanderthals have benefited from gaining modern human DNA, for example, in their version of the FOXP2 gene? “We can’t discount the possibility,” says Mark Pagel at the University of Reading, UK, but figuring it out won’t be easy because FOXP2‘s effects may have been different in Neanderthals and may not have helped them acquire the basics of language.

“It is too early to tell,” says Castellano, whose team is starting to tackle such questions. In other words, the jury is still out.

Should we fear our inner neanderthal?

Some of us have a secret in our genome: DNA that our forebears got from sex with Neanderthals. But does this DNA hold any sway over us?

A team led by Corinne Simonti at Vanderbilt University in Nashville, Tennessee, studied medical records and genetic data from more than 28,000 people of European descent. They found small but significant links between the presence of certain Neanderthal DNA segments and the incidence of medical conditions, including depression and addiction (Science, doi.org/bch3).

“The brain is incredibly complex, so it’s reasonable to expect that introducing changes from a different evolutionary path might have negative consequences,” says Simonti. However, many factors influence susceptibility to health issues, so people without this ancient DNA might still develop depression and those who do carry this DNA might never experience it.

In fact, plenty of “our” DNA has foreign origins – from extinct early humans to viruses – and can have both good and bad effects on health.

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