Aldehydes are everywhere. Graduates of high school biology may remember the distinct smell of formaldehyde, which is also used to make plastics and adhesives, but other aldehydes include vanillin, which gives vanilla its flavor, and cinnamaldehyde, which gives cinnamon its flavor.
Some, like formaldehyde, have been linked to cancer. But the mechanism by which they might cause cancer hasn't been clear, said MUSC Hollings Cancer Center researcher Natalie Saini, Ph.D.
"There's never been definitive proof of how aldehydes would cause cancer, and that's because we don't know what kind of damage they cause. So my lab's mostly been interested in trying to understand how aldehydes cause mutations," she said.
The American Cancer Society recently awarded Saini a Research Scholar Grant to look at one aldehyde in particular – acrolein. She is investigating how it might cause cancer and how it might be stopped.
Acrolein can be found in smoke – tobacco smoke, smoke from wood fires, automobile exhaust – as well as in our bodies, as a byproduct of the breakdown of lipids.
It hasn't seemed to cause DNA mutations, though. It's true that it's a weak mutagen, Saini said – except in one particular circumstance. When DNA is in a single-strand state, either because the cell is in the process of making copies of its DNA or because cellular stress has caused a buildup of single-stranded DNA, that's when acrolein can strike.
"Now there's a unique vulnerability in cells that is causing aldehyde mutagenesis. And when we give single strand DNA to cells and we put acrolein in, we can see a clear mutation increase," she said.
Diet is one factor in how much acrolein a person is exposed to. "If I'm on a high sugar, high fat diet – what they call the Western diet – then the amount of fat in the cells is a lot. When that fat gets oxidized, you get aldehydes," Saini explained.
"We started to look at what's the biggest amount of aldehyde being produced, and acrolein was one of them. So we said, 'Well let's check if this one is mutagenic.' It very much was. And now we're just trying to understand what types of mutations and how it gets fixed."
There are natural mechanisms to remove acrolein from the body. Saini's research is looking at a group of enzymes called aldehyde dehydrogenases, which break down the acrolein into nontoxic components. Defects in these aldehyde dehydrogenases could contribute to liver disease or cancer if the body can't keep up with the acrolein being produced.
Aldehyde scavengers, found in certain fruits and vegetables, also remove aldehyde.
"We're trying to test if cells were exposed to those, would that take away the mutations or damage from occurring?" she said.
Although these aldehyde scavengers can be found in foods, it's unlikely that someone could eat enough of, for example, persimmons, to make a meaningful difference. Most likely, some type of supplement would need to be developed, Saini said.
Some drugs, including the diabetes drug metformin, also remove aldehydes.
Saini's grant will continue for four years.
