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      Polycyclic aromatic hydrocarbons and PAH-related DNA adducts

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          Abstract

          Investigations on the impact of chemicals on the environment and human health have led to the development of an exposome concept. The exposome refers to the totality of exposures received by a person during life, including exposures to life-style factors, from the prenatal period to death. The exposure to genotoxic chemicals and their reactive metabolites can induce chemical modifications of DNA, such as, for example, DNA adducts, which have been extensively studied and which play a key role in chemically induced carcinogenesis. Development of different methods for the identification of DNA adducts has led to adopting DNA adductomic approaches. The ability to simultaneously detect multiple PAH-derived DNA adducts may allow for the improved assessment of exposure, and offer a mechanistic insight into the carcinogenic process following exposure to PAH mixtures. The major advantage of measuring chemical-specific DNA adducts is the assessment of a biologically effective dose. This review provides information about the occurrence of the polycyclic aromatic hydrocarbons (PAHs) and their influence on human exposure and biological effects, including PAH-derived DNA adduct formation and repair processes. Selected methods used for determination of DNA adducts have been presented.

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          Most cited references73

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          Cytochrome p450 and chemical toxicology.

          The field of cytochrome P450 (P450) research has developed considerably over the past 20 years, and many important papers on the roles of P450s in chemical toxicology have appeared in Chemical Research in Toxicology. Today, our basic understanding of many of the human P450s is relatively well-established, in terms of the details of the individual genes, sequences, and basic catalytic mechanisms. Crystal structures of several of the major human P450s are now in hand. The animal P450s are still important in the context of metabolism and safety testing. Many well-defined examples exist for roles of P450s in decreasing the adverse effects of drugs through biotransformation, and an equally interesting field of investigation is the bioactivation of chemicals, including drugs. Unresolved problems include the characterization of the minor "orphan" P450s, ligand cooperativity and kinetic complexity of several P450s, the prediction of metabolism, the overall contribution of bioactivation to drug idiosyncratic problems, the extrapolation of animal test results to humans in drug development, and the contribution of genetic variation in human P450s to cancer incidence.
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            Is Open Access

            Pulmonary Oxidative Stress, Inflammation and Cancer: Respirable Particulate Matter, Fibrous Dusts and Ozone as Major Causes of Lung Carcinogenesis through Reactive Oxygen Species Mechanisms

            Reactive oxygen or nitrogen species (ROS, RNS) and oxidative stress in the respiratory system increase the production of mediators of pulmonary inflammation and initiate or promote mechanisms of carcinogenesis. The lungs are exposed daily to oxidants generated either endogenously or exogenously (air pollutants, cigarette smoke, etc.). Cells in aerobic organisms are protected against oxidative damage by enzymatic and non-enzymatic antioxidant systems. Recent epidemiologic investigations have shown associations between increased incidence of respiratory diseases and lung cancer from exposure to low levels of various forms of respirable fibers and particulate matter (PM), at occupational or urban air polluting environments. Lung cancer increases substantially for tobacco smokers due to the synergistic effects in the generation of ROS, leading to oxidative stress and inflammation with high DNA damage potential. Physical and chemical characteristics of particles (size, transition metal content, speciation, stable free radicals, etc.) play an important role in oxidative stress. In turn, oxidative stress initiates the synthesis of mediators of pulmonary inflammation in lung epithelial cells and initiation of carcinogenic mechanisms. Inhalable quartz, metal powders, mineral asbestos fibers, ozone, soot from gasoline and diesel engines, tobacco smoke and PM from ambient air pollution (PM10 and PM2.5) are involved in various oxidative stress mechanisms. Pulmonary cancer initiation and promotion has been linked to a series of biochemical pathways of oxidative stress, DNA oxidative damage, macrophage stimulation, telomere shortening, modulation of gene expression and activation of transcription factors with important role in carcinogenesis. In this review we are presenting the role of ROS and oxidative stress in the production of mediators of pulmonary inflammation and mechanisms of carcinogenesis.
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              DNA damage and repair.

              The aesthetic appeal of the DNA double helix initially hindered notions of DNA mutation and repair, which would necessarily interfere with its pristine state. But it has since been recognized that DNA is subject to continuous damage and the cell has an arsenal of ways of responding to such injury. Although mutations or deficiencies in repair can have catastrophic consequences, causing a range of human diseases, mutations are nonetheless fundamental to life and evolution.
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                Author and article information

                Contributors
                +48 32 254 60 31 , blaszczyk@ietu.katowice.pl
                Journal
                J Appl Genet
                J. Appl. Genet
                Journal of Applied Genetics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1234-1983
                2190-3883
                12 December 2016
                12 December 2016
                2017
                : 58
                : 3
                : 321-330
                Affiliations
                [1 ]ISNI 0000 0004 0446 6422, GRID grid.418673.f, , Institute for Ecology of Industrial Areas, Environmental Toxicology Group, ; 6, Kossutha Street, 40-844 Katowice, Poland
                [2 ]Witold Pilecki State School of Higher Education, 8, Maksymiliana Kolbego Street, 32-600 Oświęcim, Poland
                Author notes

                Communicated by: Michal Witt

                Article
                380
                10.1007/s13353-016-0380-3
                5509823
                27943120
                7e36e163-1dc7-4acc-aefd-541e3a43d125
                © The Author(s) 2016

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 7 July 2016
                : 17 November 2016
                : 21 November 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004569, Ministerstwo Nauki i Szkolnictwa Wyższego;
                Award ID: N N404 11073
                Award Recipient :
                Categories
                Human Genetics • Review
                Custom metadata
                © Institute of Plant Genetics, Polish Academy of Sciences, Poznan 2017

                Genetics
                polycyclic aromatic hydrocarbons,benzo[a]pyrene,dna damage,pah–dna adducts
                Genetics
                polycyclic aromatic hydrocarbons, benzo[a]pyrene, dna damage, pah–dna adducts

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