Can Arsenic Damage Human DNA?
Researchers from the University of Wrocław will receive nearly PLN 25 million from the National Science Centre to carry out their projects as part of the OPUS 24 and SONATA 18 competitions. One of the young researchers is dr Ireneusz Litwin, assistant professor at the Academic Excellence Incubator – Research Centre for DNA Repair and Replication (Faculty of Biological Sciences, UWr). The title of his research paper, for which he will receive PLN 2,199,660 in funding, is “Map of DNA damage and repair processes induced by arsenic”.
What is the specific fascination with this particular element?
– The Department of Genetics and Cell Physiology, led by prof. Robert Wysocki, has been investigating for many years how cells uptake arsenic and how they eliminate this toxic element. When I joined prof. Wysocki’s team, the topic of arsenic intrigued me from a different perspective. Well, it turns out that millions of people worldwide consume water and food containing arsenic. Long-term exposure to arsenic is a causal factor in numerous diseases, including cancer. On a side note, research conducted in recent years by prof. Lubiński’s team at Pomeranian Medical University in Szczecin suggests that high levels of arsenic in the bloodstream constitute a strong risk factor that predisposes Polish women to develop cancer. Unfortunately, despite many years of research conducted by leading scientific institutions worldwide, the mechanism by which this element causes cancer remains elusive. Interestingly, one theory suggests that arsenic may induce DNA damage, which in turn can lead to genetic instability and the development of cancerous cells. This mode of arsenic action has piqued my interest, and thus far, my work has been focused on investigating the types of DNA damage generated by arsenic and how cells attempt to repair such damage.
As you have mentioned, despite many years of research conducted on various organisms, the exact mechanism by which arsenic leads to cancer is still not fully understood. Do your research efforts aim to unravel this unknown?
I hope that my ongoing research will contribute to understanding how arsenic exposure leads to DNA damage in humans. Unraveling such a mechanism may help determine what type of genetic background in humans may be particularly predisposed to cancer development.
What is a genomic map? And what purpose is it supposed to serve?
– In the new project, we will investigate the timing of DNA damage generation following arsenic exposure, the genomic locations where such damage occurs, and whether the site and quantity of potential DNA damage vary depending on the cell cycle phase. These questions will be indirectly addressed by examining the distribution and quantity of DNA damage throughout the entire genome, focusing on each chromosome separately. It is worth noting that chromosomes consist of various elements with distinct properties. For instance, the majority of DNA is wrapped around histones, but there are also regions where DNA is “naked”, devoid of proteins, and thus more accessible to external factors. Additionally, some parts of chromosomes undergo intense gene expression, while others do not. Lastly, DNA within telomeres contains high amounts of guanine, which may potentially be more susceptible to binding by arsenic. There are just a few examples as the analysis we will conduct will be much broader. Ultimately, we hope to create a chromosome map that illustrates which regions of the chromosome are susceptible to arsenic-induced DNA damage. We may even uncover the underlying reasons behind it.
What tools will you use in conducting your research?
Within this project, research will be conducted using the eukaryotic model organism Saccharomyces cerevisiae, commonly known as baker’s yeast, as well as human cell lines. We will employ various techniques, including molecular genetics, to label proteins, as well as to remove DNA fragments, and fluorescence microscopy, which will enable the direct colocalization of DNA damage with specific chromosomal regions. However, the majority of the research will be conducted using chromatic immunoprecipitation techniques coupled with next-generation sequencing. After obtaining the sequencing results, extensive bioinformatics work awaits us, which will provide the conclusions.
We wish you good luck!
Ed. Katarzyna Górowicz-Maćkiewicz
Translated by Ilona Mutke (student of English Studies at the University of Wrocław) as part of the translation practice.
