At its simplest, the adductome is the totality of chemical

adduct In chemistry, an adduct (; alternatively, a contraction of "addition product") is a product of a direct addition of two or more distinct molecules, resulting in a single reaction product containing all atoms of all components. The resultant is ...

s that are present in particular cellular

macromolecule A macromolecule is a "molecule of high relative molecular mass, the structure of which essentially comprises the multiple repetition of units derived, actually or conceptually, from molecules of low relative molecular mass." Polymers are physi ...

s such as

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

, and

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

, or

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s found within the organism. These adducts can detrimentally alter the chemical properties of these macromolecules and are therefore also referred to as damage. Adducts may arise as a consequence of the chemical reaction between a given "physicochemical agent to which an organism is exposed across the lifespan" (sometimes referred to as the exposome). These physicochemical agents can be exogenous in origin, and include ionizing and non-ionizing radiation, the diet, lifestyle factors, pollution, and

xenobiotic A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...

s. They may damage the macromolecules directly, or indirectly e.g., some xenobiotic substances require

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

of the xenobiotic to produce a chemically reactive

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

which can then form a covalent bond with the endogenous macromolecule. Agents that damage macromolecules can also arise from endogenous sources, such as

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

that are a side product of normal respiration, leading to the formation of oxidatively damaged DNA etc., or other reactive species e.g., reactive nitrogen, sulphur, carbon, selenium and halogen species. The term "adductome" first appeared in a journal article in 2005. Although originally the term related to adducts of DNA, the adductomic approach has now been adopted by

chemists in their attempts to identify protein adducts. More recently, this has been extended by Kanaly's group to include RNA adducts. Most recently, nucleic acid adductomics has been reported, which has to potential to study a range of DNA and RNA adducts.

DNA and RNA

DNA adducts arise from compounds that bind to

, that covalently modify the DNA, resulting in damage. This damage can result in

mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...

. These mutations can result in a variety of adverse health effects, including

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

and

birth defects A birth defect is an abnormal condition that is present at birth, regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth de ...

multicellular organisms A multicellular organism is an organism that consists of more than one cell, unlike unicellular organisms. All species of animals, land plants and most fungi are multicellular, as are many algae, whereas a few organisms are partially uni- and pa ...

. The science of adductomics seeks to identify and measure all DNA, RNA or protein adducts, identify their origins, and determine their role in health and disease. ''Cellular DNA and/or RNA adductomics'' is performed after the target

nucleic acid Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a pentose, 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nuclei ...

has been extracted from the cells (e.g., from cultured cells, or tissues). ''Urinary DNA adductomics'' non-invasively evaluates DNA adducts that are present in urine, following their

DNA repair DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is cons ...

Nucleic acid

Nucleic acid (NA) adductomics brings together DNA-, RNA- and, to some extent, protein adductomics to provide a more comprehensive view of the adduct burden to these molecules. NA adductomics builds upon previous DNA adductomics and DNA crosslinkomics (which aims to analyze the totality of DNA-DNA crosslinks ) assays and encompasses the analysis of modified (2′-deoxy)ribonucleosides (2′-dN/rN), modified nucleobases (nB), plus: DNA-DNA, RNA-RNA, DNA-RNA, DNA-protein, and RNA-protein crosslinks. Interestingly, many of these types of adducts are seen in urine from healthy humans, using ''urinary NA adductomics''. Confirmation of the presence of DNA-RNA crosslinks in urine came from a recent study that demonstrated the presence of cellular DNA-RNA crosslinks, arising from

formaldehyde Formaldehyde ( , ) (systematic name methanal) is an organic compound with the chemical formula and structure , more precisely . The compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde. It is stored as ...

exposure.

References

{{reflist DNA Oncology