April 11, 2014
Many Common Household Products Contain DNA-Damaging Nanoparticles: Study
redOrbit Staff & Wire Reports - Your Universe Online
But the current study suggests these tiny particles can be toxic to cells.
For instance, the researchers found that zinc oxide nanoparticles, often used in sunscreen to block ultraviolet rays, significantly damages DNA. Nanoscale silver, which has been added to toys, toothpaste, clothing, and other products for its antimicrobial properties, also produces extensive DNA damage.
The US Food and Drug Administration (FDA) does not require manufacturers to test nanoscale additives for a given material if the bulk material has already been shown to be safe. However, there is evidence that the nanoparticle form of some of these materials may not be safe due to their extremely small size and differences in physical, chemical, and biological properties. They can also penetrate cells more easily.
“The problem is that if a nanoparticle is made out of something that’s deemed a safe material, it’s typically considered safe. There are people out there who are concerned, but it’s a tough battle because once these things go into production, it’s very hard to undo,” said Bevin Engelward, professor of biological engineering at MIT and lead researcher of the current study.
Engleward and associate professor Philip Demokritou, director of HSPH’s Center for Nanotechnology and Nanotoxicology, used a high-speed screening technology to analyze the DNA damage caused by nanoparticles, allowing them to study the potential hazards at a much faster rate and larger scale than previously possible.
The researchers focused on five types of engineered nanoparticles — silver, zinc oxide, iron oxide, cerium oxide, and silicon dioxide (also known as amorphous silica) — that are used industrially. Some of these nanomaterials can produce free radicals called reactive oxygen species, which can alter DNA. Furthermore, once these particles get into the body, they may accumulate in tissues, causing even more damage.
“It’s essential to monitor and evaluate the toxicity or the hazards that these materials may possess. There are so many variations of these materials, in different sizes and shapes, and they’re being incorporated into so many products,” said Christa Watson, a postdoc at HSPH and the lead author of a paper about the study published in the journal ACS Nano.
“This toxicological screening platform gives us a standardized method to assess the engineered nanomaterials that are being developed and used at present,” she said.
The researchers said they hope the screening technology could also be used to help design safer forms of nanoparticles, and are already working with commercial partners to create safer UV-blocking nanoparticles.
Until now, most studies of nanoparticle toxicity have focused on cell survival after exposure, while few have examined genotoxicity – the ability to damage DNA. Although genotoxicity may not necessarily kill a cell, it can lead to cancerous mutations if the DNA damage is not repaired.
A common way to study DNA damage in cells is something called a “comet assay,” named for the comet-shaped smear that damaged DNA forms during the test. The procedure is based on gel electrophoresis, a test in which an electric field is applied to DNA placed in a matrix, forcing the DNA to move across the gel. During electrophoresis, damaged DNA travels farther than undamaged DNA, producing a comet-tail shape. Measuring how far the DNA can travel reveals how much DNA damage has taken place.
However, this procedure, while highly sensitive, is very tedious. In 2010, Engelward and MIT professor Sangeeta Bhatia developed a much more rapid version of the comet assay. Dubbed the CometChip, it uses microfabrication technology that allows single cells to be trapped in tiny microwells within the matrix, enabling as many as 1,000 samples to be processed in the time it formerly took to process just 30 samples. This allows researchers to test dozens of experimental conditions at a time, which can be analyzed using imaging software.
In the current study, the researchers used the CometChip to test the nanoparticles’ effects on two types of cells that are commonly used for toxicity studies – lymphoblastoids, a type of human blood cell, and an immortalized line of Chinese hamster ovary cells.
The results showed that zinc oxide and silver produced the greatest DNA damage in both cell lines. At a concentration of 10 micrograms per milliliter — a dose not high enough to kill all of the cells — these generated a large number of single-stranded DNA breaks, the study found.
Silicon dioxide, which is commonly added during food and drug production, generated very low levels of DNA damage, while iron oxide and cerium oxide also showed low genotoxicity.
The researchers said additional studies are needed to determine how much exposure to metal oxide nanoparticles is safe for humans.
“The biggest challenge we have as people concerned with exposure biology is deciding when is something dangerous and when is it not, based on the dose level. At low levels, probably these things are fine,” Engelward said. “The question is: At what level does it become problematic, and how long will it take for us to notice?”
One of the greatest areas of concern is nanoparticle exposure among children and fetuses, who may be more vulnerable to DNA damage because their cells divide more frequently than adult cells do. Occupational exposure to nanoparticles is also an important area of concern.
The researchers said the most common routes that engineered nanoparticles follow into the body are through the skin, lungs, and stomach. They are currently investigating nanoparticle genotoxicity on those types of cells, along with studying the effects of other engineered nanoparticles.