Carcinogenicity was tested on hepatocytes
Human cells were used to determine the carcinogenicity of substances
Researchers from the Massachusetts Institute of Technology have come up with a new screening method that is faster, simpler and more accurate than existing tests to determine whether a particular substance can cause cancer.
The scientists' article was published in the journal Nuclear Acids Research (Ngo et al., Sensitive CometChip assay for screening potentially carcinogenic DNA adducts by trapping DNA repair intermediates).
Currently, according to researchers, about 80 thousand chemicals are used in the industry. For the vast majority of them, there is very little or no information at all about carcinogenicity – the ability to cause cancer.
Today, to determine the carcinogenic activity, scientists use a chemical substance on mice, and then monitor whether they have cancer. This method takes about two years. But a new test developed by American scientists can speed up and simplify this process.
The device created earlier by researchers was called CometChip. It detects DNA damage, which can be used to judge the occurrence of cancer. To do this, DNA is placed in an array of trace elements on a polymer gel plate, and then exposed to an electric field. The strands of DNA that have been damaged go towards one of the poles of the electric field, creating a comet-like tail.
Although CometChip is good at detecting breaks in DNA, as well as their damage, which is easily converted into breaks, it cannot detect another type of damage. They are formed when chemicals combine with a DNA strand and distort the structure of the double helix, preventing gene expression and cell division.
This kind of damage is caused by some chemicals. For example, aflatoxin, which is produced by mushrooms and can enter peanuts and other crops, as well as benzo [a]pyrene, which can be formed during cooking at high temperatures.
In their new work, the scientists decided to try to adapt CometChip so that it could detect this type of DNA damage. To do this, the authors performed DNA repair of cells to generate strand breaks. Usually, when a cell detects the addition of foreign chemicals and the subsequent distortion of the DNA structure, it tries to repair it by cutting out the damage and then replacing it with a new piece of DNA.
To capture these broken strands, the researchers treated the cells with two compounds that prevent them from synthesizing new DNA. This stops the repair process and causes the synthesis of unrepaired single-stranded DNA, which the test can detect. Scientists called the modified device HepaCometChip and tested it on human liver cells.
First, they irradiated hepatocytes with ultraviolet radiation, which is guaranteed to cause DNA damage leading to the development of cancer. After that, HepaCometChip was able to find these changes. Then the scientists tested how different chemicals act on the DNA of cells. It turned out that all of them coincide with the data obtained earlier by laboratory methods. The next goal of scientists is to check for carcinogenicity of a wide group of chemical compounds that have previously been tested by standard methods.
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