Applications of Adductomics in Chemically Induced Adverse Outcomes and Major Emphasis on DNA Adductomics: A Pathbreaking Tool in Biomedical Research

Abstract

Adductomics novel and emerging discipline in the toxicological research emphasizes on adducts formed by reactive chemical agents with biological molecules in living organisms. Development in analytical methods propelled the application and utility of adductomics in interdisciplinary sciences. This review endeavors to add a new dimension where comprehensive insights into diverse applications of adductomics in addressing some of society's pressing challenges are provided. Also focuses on diverse applications of adductomics include: forecasting risk of chronic diseases triggered by reactive agents and predicting carcinogenesis induced by tobacco smoking; assessing chemical agents' toxicity and supplementing genotoxicity studies; designing personalized medication and precision treatment in cancer chemotherapy; appraising environmental quality or extent of pollution using biological systems; crafting tools and techniques for diagnosis of diseases and detecting food contaminants; furnishing exposure profile of the individual to electrophiles; and assisting regulatory agencies in risk assessment of reactive chemical agents. Characterizing adducts that are present in extremely low concentrations is an exigent task and more over absence of dedicated database to identify adducts is further exacerbating the problem of adduct diagnosis. In addition, there is scope of improvement in sample preparation methods and data processing software and algorithms for accurate assessment of adducts.

Keywords: DNA adduct; adductomics; cancer detection tool; protein adduct.

Figure 1

Schematic representation of how chemical agents reacts with DNA, RNA and proteins in cells and leading formation of respective adducts, followed by their resulting in toxicological outcomes. In the figure ① indicating the exposure to toxicant ② at cellular level due to enzymatic activity production reactive species or metabolites which are highly reactive than parent molecule ③ generated reactive molecules interact with various cellular components such as protein, RNA and DNA and leading to cause of various pathological outcomes.

Figure 2

Three types of adducts are formed in biological systems (or organisms) when exposed to chemical agents and their associated health hazards. The adducts (A, B, C, and D) are identified using a fragmentation pattern in the LC-MS spectra. In DNA adducts, the characteristic peaks from the protonation events (M + H) + and cleavage events (M + H−116) + are detected. In RNA adducts, the characteristic peaks are detected from the protonation (M + H)+ and cleavage events (M + H−132)+ [20,21]. To identify the protein adducts, we generally compare the spectra data of unknown compounds with the reference adduct. Reference adducts would be synthesized by assuming an electrophile, and they should be compared with the unknown adducts of interest. By adding proposed precursor electrophiles to plasma or whole blood/lysate the reference adducts can be generated, and they are subjected to fragmentation using LC-MS. The synthetic adducts then further will be compared with the novel or unidentified adducts with m/z of the precursor ions, also studying fragmentation patterns and retention times. On the other hand, by using UNIMOD database that lists the protein modifications is also used to identify the adducts [22].

Figure 3

Application of adductomics in precision medicine of anticancer drugs for better targeting and reducing the toxicity.