Today, cancer constitutes many of the most serious and common medical diagnoses. Though its causes and characteristics can be diverse, most cancers occur when the DNA contained in human cells is mutated. These mutations, or changes in the genetic blueprints of a patient, can create a DNA sequence that causes cells to replicate uncontrollably, sometimes growing into invasive tumors and creating signals and interactions that interfere with the body’s function.
Mutations are generally considered to be the start of cancer – they can arise randomly as a result of errors that occur during the process of DNA replication, but they can also be caused by interactions within our environment and our lifestyles. Certain chemicals and materials have been identified as being mutagenic, or having properties that tend to cause genetic changes to occur. Exposure to these chemicals, and even sunlight, can cause damage to DNA, and mutations can occur in the process of the body’s efforts to repair the damage.
(see: https://www.youtube.com/watch?v=8BJ8_5Gyhg8 )
To help reduce risk and increase awareness of cancer and its causes, scientists work to identify cancer-causing substances and materials (mutagens) so that exposure can be limited or regulated. One does not have to rely on extensive documentation of occurrences in which individuals developed cancer after having interacted with or being exposed to the mutagen; instead, a variety of methods have been developed that allow scientists to identify these mutagens safely in the laboratory.
One of the most common methods for detecting the mutagenic properties of a compound is using a procedure called the Ames Test. This is a widely accepted technique because it is rapid, inexpensive, and simple to apply (2). In the Ames Test, a sample of living bacteria is allowed to thrive and is then exposed to the substance (1). The bacterial species used can be chosen based on known characteristics that can be measured, such as the ability to break down certain sugars or proteins. A change in a bacteria’s ability to process a nutrient after exposure to the suspected mutagen can suggest that a mutation has occurred in the bacteria’s DNA, rewriting its genetic sequences and disabling that characteristic.
For most purposes, the Ames Test is a useful analytical tool and provides a helpful assessment of a chemical compound’s interaction with the genetic makeup of living organisms. The bacteria serve as a model for human cells, allowing scientists to predict whether a substance will have a negative effect on human health without having to endanger human subjects in the first place. However, though bacterial and human DNA is made up of the same fundamental building blocks, there are disparities in the biology of bacteria and humans, comparatively, as well as in how DNA functions.
Recently, despite the convenience that the Ames Test offers, studies have begun to explore alternative methods to increase the applicability and accuracy of mutagen tests in the context of human health. This research has sought predominantly to find an alternative analysis technique similarly convenient and inexpensive to the Ames Test that utilizes human or animal cells as the subject- instead of bacteria – to better model human biology.
One alternative procedure has shown promise: originally also used to detect mutations in bacteria, the Genome Profiling-Based Mutation Assay (GPMA) has recently been shown to yield results similarly accurate to the Ames Test in application to mammalian tissue cells (3). Additionally, the Ames Test detects mutations based on changes in specific regions of the DNA, such as those responsible for a bacterial species’ ability to process certain nutrients, whereas GPMA involves mapping all of an organism’s genetic information before and after exposure to a suspected mutagen and comparing them. With this method, the number of mutations that occur can determined, as well as their location within the genome (4).
A crucial step in the fight against cancer is understanding the mutations cancer can stem from and how these mutations are caused. An essential aspect of this obstacle is being able to identify the specific mutations and their mutagens that can cause cancer to develop. Though the Ames Test is useful for anticipating potential mutagenic chemicals, GPMA is one of the many methods being explored for use on animal cells and can characterize the effects of a mutagen with higher specificity. With improved methods of detecting mutations, we will be able to minimize human exposure to cancer-causing mutagens and reduce cancer’s impact.
For more information, discover these resources:
- Akyil, D., Konuk, M., Eren, Y., Liman, R., and Sağlam, E. (2017) Mutagenic and genotoxic effects of Anilofos with micronucleus, chromosome aberrations, sister chromatid exchanges and Ames test. Cytotechnology. 69, 865–874
- Barbezan, A. B., Martins, R., Bueno, J. B., and Villavicencio, A. L. C. (2017) Ames Test to Detect Mutagenicity of 2-Alkylcyclobutanones: A Review. Journal of Food Science. 82, 1518–1522
- Kumari, P., Gautam, S. G., Baba, M., Tsukiashi, M., Matsuoka, K., Yasukawa, K., and Nishigaki, K. (2017) DNA-based mutation assay GPMA (genome profiling-based mutation assay): reproducibility, parts-per-billion scale sensitivity, and introduction of a mammalian-cell-based approach. The Journal of Biochemistry. 162, 395–401
- Kumari, P., Kamiseki, M., Biyani, M., Suzuki, M., Nemoto, N., Aita, T., and Nishigaki, K. (2014) Detection of ultra-low levels of DNA changes by drinking water: epidemiologically important finding. The Journal of Biochemistry. 157, 113–119
The Science of Blogging 