Introduction to Adductomics
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The risk of disease is affected by internal and external environmental factors that an individual is exposed to throughout their lifespan, such as diet, pollution, diseases, and lifestyle choices. Collectively, this is know as the exposome. From conception, humans can encounter a wide variety of stressors in the form of tobacco smoke, sunlight, drugs, food, and water contaminants, in addition to their own body's metabolism. These exposure elements have the capacity to induce damage or modifications, known as adducts, to nucleic acids (i.e., DNA, RNA and the nucleotide precursor pools), and proteins. These adduct can are understood to play a major role in the development of illnesses such as cancer, neurodegenerative diseases, cardiovascular diseases, and others. Given that the exposome describes the total exposures that an individual encounters across the lifespan, it is critical that develop methods to comprehensively assess the physicochemical agents to which we are exposed and use this information to better understand disease risk. |
Role of the exposome in the generation of cellular molecular modifications.
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Areas of research
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Nucleic Acid Adductomics
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Protein Adductomics
Electrophilic compounds in our bodies can come from two main sources: stuff we make ourselves (like when our cells get stressed out) and things we take in from the outside (like food and medicine). These reactive substances can mess with important parts of our cells, like our DNA and proteins, which can be bad for our health. Because these compounds don't stick around for long, it's tricky to measure them directly. Scientists have been working since the 1970s to develop ways to detect them by looking at the changes they make to certain proteins found in our blood. When these electrophiles react with proteins, they form what's called "adducts," chemical tags which can give us clues about how much we've been exposed to these reactive substances over time. As part of this branch of focus, protein adductomics aims to use untargeted and targeted methods to investigate modification of proteins by endogenous or exogenous sources.
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Genome-wide Mapping of DNA Damage
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Resources about Adductomics
To better serve our community, IAC is committed and encourages the exchange of information worldwide.
Below are resources from the different areas of research in adductomics.
Protein adductomics
Funk, W., Montgomery, N., Bae, Y., Chen. J., Chow, T., Martinez, M., Lurmann, F., Eckel, S., McConnell, R., Xiang, A. (2021) HSA-Cys34 Adducts in Newborn Dried Blood Spots: Associations with Air Pollution Exposure During Pregnancy. Frontiers in Public Health, 9, 1-9.
Grigoryan, H., Edmands, W., Lu, SS., Yano, Y., Regazzoni, L., Iavarone, AT., Williams, ER., Rappaport, SM. (2016) Adductomics Pipeline for Untargeted Analysis of Modifications to Cys34 of Human Serum Albumin. Anal Chem. 2016 Nov 1;88(21):10504-10512.
Rappaport, S., He, L., Grigoryan, H., Funk, W., Williams, E. (2012) Adductomics: Characterizing Exposures to Reactive Electrophiles. Toxicology Letters, 13;213(1), 83-90.
Dagnino S., Bodinier B., Grigoryan H., Rappaport S.M., Karimi M., Guida F., Polidoro S., Edmands W.B., Naccarati A, Fiorito G., Sacerdote C., Krogh V., Vermeulen R., Vineis P., Chadeau-Hyam M (2020) Agnostic Cys34-albumin adductomics and DNA methylation: implication of N-acetylcysteine in lung carcinogenesis years before diagnosis. International Journal of Cancer, 146, 3294-3303.
Preston G., Dagnino S., Ponzi E., Sozeri O., van Veldhoven K., Baratta B., Liu S., Grigoryan H., Lu S., Rappaport S., Chunge K.F., Cullinan P., Sinharayg R., Kelly F., Chadeau-Hyam M., Vineis P., Phillips D (2020). Relationships between airborne pollutants, serum albumin adducts and short-term health outcomes in an experimental crossover study. Chemosphere, 239, 124667.
Vineis P., Robinson O., Chadeau-Hyam M, Dehghan A., Mudway I., Dagnino S (2020). What’s new in the Exposome? Environment International, 143, 105887.
Grigoryan H., Shiffman C., Gunter M.J, Dagnino S., Naccarati A., Polidoro S., Dudoit S., Vineis P. Rappaport S.M (2019). Cys34 Adductomics Provides Evidence Linking Colorectal Cancer with Redox Biology and the Gut Microbiota. Cancer Research, 79 (23), 6024-6031.
Liu S., Grigoryan H., Edmands WMB, Dagnino S., Sinharay R., Cullinan P., Collins P., Chung K.F., Barratt B., Kelly F.J., Vineis P., Rappaport S.M (2018). Cys34 adductomes differ between patients with chronic lung or heart disease and healthy controls in central London. Environmental Science and Technology 52 (4) 2307-2313.
Funk, W., Montgomery, N., Bae, Y., Chen. J., Chow, T., Martinez, M., Lurmann, F., Eckel, S., McConnell, R., Xiang, A. (2021) HSA-Cys34 Adducts in Newborn Dried Blood Spots: Associations with Air Pollution Exposure During Pregnancy. Frontiers in Public Health, 9, 1-9.
Grigoryan, H., Edmands, W., Lu, SS., Yano, Y., Regazzoni, L., Iavarone, AT., Williams, ER., Rappaport, SM. (2016) Adductomics Pipeline for Untargeted Analysis of Modifications to Cys34 of Human Serum Albumin. Anal Chem. 2016 Nov 1;88(21):10504-10512.
Rappaport, S., He, L., Grigoryan, H., Funk, W., Williams, E. (2012) Adductomics: Characterizing Exposures to Reactive Electrophiles. Toxicology Letters, 13;213(1), 83-90.
Dagnino S., Bodinier B., Grigoryan H., Rappaport S.M., Karimi M., Guida F., Polidoro S., Edmands W.B., Naccarati A, Fiorito G., Sacerdote C., Krogh V., Vermeulen R., Vineis P., Chadeau-Hyam M (2020) Agnostic Cys34-albumin adductomics and DNA methylation: implication of N-acetylcysteine in lung carcinogenesis years before diagnosis. International Journal of Cancer, 146, 3294-3303.
Preston G., Dagnino S., Ponzi E., Sozeri O., van Veldhoven K., Baratta B., Liu S., Grigoryan H., Lu S., Rappaport S., Chunge K.F., Cullinan P., Sinharayg R., Kelly F., Chadeau-Hyam M., Vineis P., Phillips D (2020). Relationships between airborne pollutants, serum albumin adducts and short-term health outcomes in an experimental crossover study. Chemosphere, 239, 124667.
Vineis P., Robinson O., Chadeau-Hyam M, Dehghan A., Mudway I., Dagnino S (2020). What’s new in the Exposome? Environment International, 143, 105887.
Grigoryan H., Shiffman C., Gunter M.J, Dagnino S., Naccarati A., Polidoro S., Dudoit S., Vineis P. Rappaport S.M (2019). Cys34 Adductomics Provides Evidence Linking Colorectal Cancer with Redox Biology and the Gut Microbiota. Cancer Research, 79 (23), 6024-6031.
Liu S., Grigoryan H., Edmands WMB, Dagnino S., Sinharay R., Cullinan P., Collins P., Chung K.F., Barratt B., Kelly F.J., Vineis P., Rappaport S.M (2018). Cys34 adductomes differ between patients with chronic lung or heart disease and healthy controls in central London. Environmental Science and Technology 52 (4) 2307-2313.
