DNA is the “machine code” of our cells – it tells the cell how to function, and therefore is responsible for our bodies working properly. However, if DNA is damaged, the code may change, and the instructions to the cells altered, making them behave abnormally. This can lead to major diseases, such as cancer, neurodegenerative and cardiovascular disease, together with aging.
The environment in which humans live represents about 90% of the risk of developing these diseases, with genetics accounting for the rest. Exposure to certain elements in the environment, such as pollution, sunlight, tobacco smoke, and certain foods, can damage DNA, creating what are known as DNA adducts, which are responsible for changing the machine code. The presence of these adducts in our cells is therefore linked to the risk of developing disease.
There are hundreds, perhaps thousands, of different adducts, but scientists have been able to study them only one at a time, so they fail to get an accurate picture of what is going on inside the cell. However, a new tool is emerging, which is called DNA adductomics. This tool enables scientists to look at all the adducts present in DNA simultaneously, and therefore offers the potential to better assess all the environmental agents to which humans are exposed, across the lifespan. With such a tool, we are better placed to assess disease risk, and this might represent a significant breakthrough for determining cancer risk.
It was previously thought that only top end, analytical techniques are suitable for DNA adductomic analysis which, due to high cost, had limited widespread use.
As part of his NIEHS-funded R01 (ES030557), awarded to principal investigator Dr. Marcus S. Cooke, together with colleagues from Chung Shan Medical University (Taiwan), it was reported that a more popular/accessible analytical technique could be used for DNA adductomics, when combined with an innovative use of a statistical analysis.
These findings will open up the DNA adductomics field, and accelerate discoveries related to environmental exposures and cancer risk. Work is ongoing to establish and utilize this powerful technique at the University of South Florida (USF) and to integrate with the numerous efforts to tackle human disease across USF, in conjunction with Moffitt Cancer Center.
The findings were published in the journal Chemosphere:
Chang, Y-J., Cooke, MS., Chen, Y-R., Yang, S-F., Lia, P-S., Hu, C-W., and Chao, M-R. (2021) Is high resolution a strict requirement for mass spectrometry-based cellular DNA adductomics? Chemosphere, 274, 129991-
The above is just part of our on-going, pioneering work in the field of DNA adductomics, which include the ability to assess an individual’s DNA adductome profile in urine, which will revolutionise the field.
Chang, Y-J., Cooke, MS., Hu, C-W. and Chao, M-R. (2018) Novel approach to integrated DNA adductomics for the assessment of in vitro and in vivo environmental exposures. Archives of Toxicology. 92, 2665-2680.
Cooke, MS., Chao, M-R., Chang, Y-J. and Hu, C-W. (2018) Urinary DNA Adductomics – A Novel Approach for Exposomics. Environment International. 121, 1033-1038.
Cooke, MS., Hu, C-W. and Chao, M-R. (2019) Editorial: Mass Spectrometry for Adductomic Analysis. Frontiers Chemistry.
Hu, C-W., Chang, Y-J., Cooke, MS. and Chao, M-R. (2019) DNA crosslinkomics: a tool for the comprehensive assessment of inter-strand crosslinks using high resolution mass spectrometry. Analytical Chemistry. 91, 15193-15203.
Guo, J., Turesky, RJ., Tarifa, A., DeCaprio, AP., Cooke, MS., Walmsley, SJ. and Villalta, PW. (2020) Development of a DNA Adductome Mass Spectral Database. Chemical Research in Toxicology, 33, 4, 852-854.
More general information about DNA adductomics can be found here:
Urinary DNA Adductomics: The Next Generation of Omics Technology | Technology Networks