It may take the bitter edge off that coffee you’re drinking or tame your lemonade’s tartness, but too much sugar will leave you feeling none too sweet.
|John Termini studies mutations that can result from high blood sugar levels such as those found in diabetes. (Photo by Markie Ramirez)|
Table sugar is made of two simpler sugars — glucose and fructose. And researchers have long known that high blood levels of that first sugar, glucose, can lead to harmful changes to important biological molecules. These changes are at the root of many of the complications seen in people with diabetes.
Now, City of Hope researchers have discovered how an altered form of DNA arising from high blood glucose levels can cause genetic mutations. And these mutations may lead to cancer and other life-threatening diseases.
Scientists have focused heavily on harmful products that form when glucose interacts with proteins. But less is understood about the sugar’s impact on DNA. So researchers led by City of Hope’s John Termini, Ph.D., professor in City of Hope’s Department of Molecular Medicine, have turned their focus to a molecule called CEdG.
CEdG results when high levels of glucose form byproducts that react with DNA, the molecule that contains the genetic instructions for life.
In previous research, the scientists found that CEdG interfered with cells’ ability to properly read their genetic code. It also hindered cells’ ability to replicate their DNA during growth.
The results suggested CEdG could cause the cells’ chromosomes to become unstable and lead to mutations, Termini said. Mutations often can disrupt normal cell function and lead to diseases, including cancer.
To test their theory, the team genetically changed cells to contain higher amounts of CEdG. They then compared how often genetic mutations appeared in those cells versus in normal, unaltered cells.
The scientists found that cells with CEdG had higher mutation levels than cells without it.
But the researchers didn’t stop there. They wanted to understand just how CEdG increased mutations. So they also tested another type of cell that was missing one of the tools needed to fix damaged DNA and prevent cancer.
The tool is called nucleotide excision repair, and the team found that CEdG produced far more mutations in cells that didn’t have it than in normal cells. [Click here for a brief video explaining nucleotide excision repair.]
So the team’s success was twofold: They showed that CEdG causes mutations, and they found the specific cellular tool — nucleotide excision repair — that cells use to fix the damage CEdG causes.
Ultimately, the findings also add to a growing body of evidence suggesting a link between cancer and metabolic diseases like diabetes.