Scientists Identify Tobacco Damages DNA Throughout The World
Scientists Identify Tobacco Damages DNA. Researchers from the University of North Carolina’s School of Medicine have developed the first high-resolution method of mapping out smoking-induced DNA damage. The technique will help us better understand the risks posed by smoking, how it leads to the appearance of cancers, why some people seem more vulnerable or resistant to cancers, and even how these cancers might be prevented.
Scientists Identify Tobacco Damages DNA and the link between smoking, Damages DNA, and lung cancers has been well established for decades now, despite what tobacco companies would have you believe. But pinpointing the exact areas of the genome impacted by smoking has so far proved beyond our capabilities, mostly because DNA is really tiny. Now, a team from the UNC School of Medicine have found a way to do just that.
Led by Aziz Sancar, MD, Ph.D., the Sarah Graham Kenan Professor of Biochemistry and Biophysics at UNC’s School of Medicine and 2015 Chemistry Nobel Prize co-laureate, they focused their attention on the major carcinogen in cigarette smoke — benzo[α]pyrene. The team developed a method to map out where this compound ties to DNA by looking at which bits of our genomes undergo repairs following exposure.
“This is a carcinogen that accounts for about 30 percent of the cancer deaths in the United States, and we now have a genome-wide map of the damage it causes,” said Sancar.
“It would be good if this [map] helps raise awareness of how harmful smoking can be,” he added. “It also would be helpful to drug developers if we knew exactly how Smoking Damages DNA is repaired throughout the entire genome.”
Mind the BaP
For all its villainous effect, Benzo[α]pyrene (BaP) is a surprisingly common substance. It’s part of the polycyclic aromatic family of hydrocarbons (i.e. multi-ringed carbon- and hydrogen- based substances,) which can form from something as innocuous as burning organic compounds all the way to the cold recesses of outer space. They’re so commonplace, in fact, that they’re theorized to have hitched rides on comets and jump-start RNA synthesis, thereby seeding life on Earth.
So it might’ve been great for news for life back in the day, but BaPs pose a serious environmental hazard to complex life. Being so common, organisms have evolved to work around BaP at the levels ambient sources (forest fires, a campfire, or an engine) can churn into our environments, but cigarette smoke delivers a huge dose (more than three times the levels of regular smoke) of the compounds directly into our lungs. Not good.
To keep us safe from environmental hazards, our bodies break down toxic compounds into smaller, inert molecules all the time. What happens with BaP is that this process breaks it down into stuff called benzo[α]pyrene diol epoxide (BPDE), which is actually more toxic than the initial hydrocarbon. BPDE chemically ties to DNA, forming a very strong bond (called an adduct) with guanine, one of the four nucleotide bases.
This alters the base enough that it becomes unreadable, so an affected cell won’t be able to synthesize the proteins it encodes or pass on the information to its offspring. All that’s needed for cancer to spring up is for the gene in question to be a tumor suppressor gene, for example. Lab trials with mice have shown that even a moderate dose of BaP applied to the animals’ skin would virtually guarantee the appearance of tumors. That’s why BaP and BPDE, via smoking, are considered to be the most important cause and multiplier factors for lung cancers.
To see exactly where in the genome BaP wrecks havoc, the team applied some of the findings on the DNA repair process which won Sancar a share of the 2015 Nobel Prize for Chemistry. Known as nucleotide excision repair, it involves certain proteins which cut out an affected strand of DNA, following which DNA-synthesizing enzymes take over and re-build the strand starting from the opposing helix.Keeping an eye on the whole genome to see where this process takes place would be impossible. So what the researchers did instead was to scour the cell for the affected strands, which would simply float around to be recycled during the repair process. These bits of code were tagged chemically, retrieved, and sequenced. Fitting all the sequences together gave the team a map of all the spots where DNA was damaged by smoking and currently under damage.
“This new method can be applied to any type of Smoking Damages DNA that involves nucleotide excision repair,” Sancar said.
Still, given the expenditure and sheer workload that goes into DNA sequencing, the proof-of-concept map the team has published doesn’t have the best resolution possible. But it does show that such maps, which can help understand the relationship between disease and what Damages DNA, are feasible. In the future, they could help uncover what dose of a particular substance can overwhelm our natural ability of nucleotide repair, which genes or gene variants help promote solution for what Damages DNA, to repair, and if there are any particular areas where the damage is harder to repair.
From their prototype map, the team was able to show that BPDE-related repairs tend to occur more often when the guanine it ties to is next to a cytosine, rather than a thymine or adenine — suggesting these areas are high-risk or “hotspot” areas for BPDE-induced mutations.
“I’m certain,” added Sancar, “that all this information will lead to a better understanding of why certain people are predisposed to cancer, and which smoking-related mutations lead to lung cancer specifically.”
Sancar also hopes that their highly specific evidence of smoking’s harm at the cellular level might convince some smokers to kick the habit. There are about 40 million smokers in the United States and over a billion worldwide.
Smoking damages DNA, altering more than 7,000 genes
The Harvard Medical School researchers tracked DNA modifications in 16,000 current and ex-smokers who had participated in various studies involving smoking, some of which go as far back as 1971. Besides filling questionnaires about smoking, diet, lifestyle and their health histories, the blood of each participant was collected and had its DNA extracted for sequencing.
The results suggest smokers have a pattern of methylation changes that affected more than 7,000 genes. Methylation modifies the function of a gene, either changing the way it functions or by (in)activating it.
“Our study has found compelling evidence that smoking has a long-lasting impact on our molecular machinery, an impact that can last more than 30 years,” said Roby Joehanes of Hebrew SeniorLife and Harvard Medical School.
With such a huge number of genes affected by smoking, it’s no wonder that smokers are highly at risk of developing heart disease and cancer, both caused by genetic damage.
Now, if all of this might sound highly concerning for those of you who stop smoking, there is some good news. The researchers say that results that Damages DNA is permanent. In fact, most of the damage disappeared in people who had stopped smoking for at least five years. Some genes, including the TIAM2 gene linked to lymphoma, still had changes caused by smoking 30 years later, as reported in the journal Circulation: Cardiovascular Genetics.
You should know
Smoking is the most contributor to preventable illnesses, killing four hundred and eighty thousand Americans yearly and roughly six million people worldwide.
While smoking was very popular in the United States, the habit has been kicked by the nation. Only 15 percent of American adults and 11 percent of high school teenagers smoke nowadays.
“These results are important because methylation, as one of the mechanisms of the regulation of gene expression, affects what genes are turned on, which has implications for the development of smoking-related diseases,” says Dr. Stephanie J. London, the deputy chief of the Epidemiology Branch at the National Institute of Environmental Health Sciences.
“Equally important is our finding that even after someone stops smoking, we still see the effects of smoking on what directly Damages DNA,” she adds.