Xenobiotics in Chemical Carcinogenesis: Translational Aspects in Toxicology

Description

Xenobiotics in Chemical Carcinogenesis: Translational Aspects in Toxicology covers the translational toxicology of xenobiotics substances in carcinogenesis by explaining the toxicokinetic and toxicodynamic, toxicogenomic, biotransformation, and resistance mechanisms in the human body. The book begins with a historical review and link to future prospects for chemical carcinogenesis. It discusses major environmental xenobiotics and their risks in inducing cancer, along with content on toxic xenobiotics and their routes of exposure in humans, the role of xenobiotic metabolism in carcinogenesis, and the toxicokinetic and toxicodynamic of xenobiotics in cancer development. Lastly, the book explores current achievements such as using toxicogenomics for predicting the carcinogenicity of xenobiotic substances and the challenges posed by carcinogenic xenobiotic substances when examining preventive methods, diagnosis, and the development of anticancer drugs for specific toxicants. Cover Xenobiotics in Chemical Carcinogenesis Copyright Dedication Contents Preface 1 Historical review and future prospective of chemical carcinogenesis Introduction Cancer caused by mutation or environmental factors Potential of carcinogens Early studies for identification of carcinogens Carcinogenesis models Theories for chemical carcinogenesis Bioassay of carcinogens Issues with carcinogenic and noncarcinogenic categorization of chemicals Long-term bioassays Chemical carcinogenesis and genetically engineered models Genetic modifiers of cancer Future of chemical carcinogenesis References 2 Xenobiotic metabolism(s) in carcinogenesis Introduction Function of aryl hydrocarbon receptors AhR in humans The AhR as a cofactor in carcinogenesis Mechanisms associated with cancer initiation Role of cytochrome P450 in the biotransformation of xenobiotics in carcinogenesis Modulation of xenobiotic-metabolizing enzymes by transcription factors Formation of carcinogenic xenobiotics during food processing Role of pesticides in breast cancer progression Conclusions References 3 Recalcitrant toxic xenobiotics and their routes of exposure to humans Introduction Recalcitrant xenobiotic molecules Halocarbons Polychlorinated Biphenyls Synthetic Polymers Alkylbenzyl Sulfonates Oil Mixtures Other Xenobiotic Compounds Routes of xenobiotic exposure Inhalation Skin (or eye) absorption Ingestion Injection Hazards from xenobiotic molecules Xenobiotics in carcinogenesis Removal of xenobiotics molecules Risk assessment for exposure of humans to toxic compounds Exposure to food carcinogens Assessment of exposure to food carcinogens Cellular adaptation to xenobiotic compounds Detection of xenobiotic-induced toxicity Human biomonitoring in the assessment of common population exposure to xenobiotics Challenges of human biomonitoring Conclusions and future prospective References 4 Incidences of crucial environmental xenobiotics for inducing cancers Introduction Pesticides in carcinogenesis Role of environmental agents in human cancer Exposure of biomarkers and assessment of human exposures Conclusions References 5 Toxicokinetics and toxicodynamics of xenobiotics in cancer development Introduction Role of toxicokinetics and toxicodynamics in risk assessments In silico approach to risk assessment Bayesian population approach to toxicokinetic/toxicodynamic models in risk analysis Bayesian population methods An illustration of Bayesian population toxicokinetic-toxicodynamic modeling in risk analysis Systematical implication of effective biomarkers in population and occupational biomonitoring The pivotal function of xenobiotic receptors and cytochrome P450 induction in toxicokinetics and toxicodynamics Potential differentiation of sex in human and animal toxicology Adverse drug reactions Body composition Sex hormones and their exemplification Growth hormone Exposure Endocrine disruption Genotoxic and nongenotoxic mechanisms of xenobiotics in carcinogenesis Advanced approaches in the science of xenobiotic toxicology Conclusions References 6 Mechanism of oxidative stress in carcinogenesis induced by xenobiotics Introduction Oxidative DNA damage Modification of gene expression Endogenous factors of ROS Exogenous sources of ROS Arrays of oxidative stress Oxidative stress linked with xenobiotic compounds in carcinogenesis Xenobiotic-induced ROS generation in embryos Oxidative stress-associated mechanisms with xenobiotics in anemia cells Time-dependent cellular adaptations to oxidative stress in normal cells Impact of ROS and RNS on the tumor microenvironment Role of oxidative stress in the treatment and prevention of cancer Anticancer drug therapy and oxidative stress Preventive and therapeutic potential of antioxidants Relationship of ROS, ncRNA, and p53 Cancer microenvironment and oxidative stress Oxidative stress and ER activity Quantitative determination of oxidative stress in cancer cells via gene expression Conclusion and future prospective References 7 Genotoxic and non-genotoxic activities of xenobiotics in carcinogenesis Introduction How to identify the mode of action of carcinogenic chemicals? Background DNA lesions Formation of DNA adducts in endogenous processes Alkylating compounds arising from endogenous processes Carcinogenic mode of action How to identify the mode of action of non-carcinogenic compounds? Mode of action for endocrine modifiers Endocrine modifiers Non-receptor regulators endocrine modifiers Tumor promotion Toxicity and inflammation at the tissue level Cytotoxicity and immune inhibition Suppression of gap-junction intercellular communications Other mechanisms Conclusions References Further reading 8 Modulation of the epigenome by xenobiotics in cancer Introduction DNA methylation in development of cancer Regulation of the epigenome by xenobiotics Carcinogenicity of Ochratoxin A through complex network of epigenetics Alteration of the epigenome by chemical carcinogens Epigenetic impacts of ethanol on liver and gastrointestinal system Alcohol-stimulated epigenetic modifications in the liver and gastrointestinal tract Changes in miRNAs Mode of alterations in DNA methylation Epigenetic effect of cadmium Epigenetics modification in lung cancer of smokers Xenobiotic-induced epigenetic remodeling Molecular pathways of epigenetic remodeling by xenobiotics Altering donors for epigenetic remodeling Modifying DNA or chromatin remodeling enzyme function and expression Xenobiotic epigenetic toxicity and the circadian clock Model systems and biomarkers to assess epigenetic effects Natural genetic variation and interaction with the epigenome at the population level Nonrodent models for epigenetic assessment Stem cells and reprogramming Novel epigenetic biomarkers for safety assessment Conclusions and perspectives References 9 Carcinogenic effects of nanomaterials with an emphasis on nanoplastics Introduction Generation of nanoplastic in the environment Effect of nanoplastics on human health Major paths of human exposure to nanomaterials Drinking water Food chain: marine products Dermal exposure: water and cosmetics Inhalation: air Cellular uptake and intracellular consequences of nanoplastic materials Major toxic impact of nanoplastics on human health Inflammation Oxidative stress and apoptosis Metabolic Homeostasis Carcinogenic impacts of nanomaterials Nano-metal elements Carcinogenic impacts of nickel NPs Carcinogenic impacts of silver NPs Nano-metal oxides Carcinogenic impacts of Titanium dioxide NPs (TiO2NPs) Carcinogenic impacts of zinc oxide NPs (ZnO NPs) Conclusions and outlook References 10 Endocrine disruptor activity of xenobiotics in carcinogenesis Introduction Endocrine disruption of xenobiotic exposure Xenoestrogens, xenoandrogens, antiestrogens, and antiandrogens Xenoestrogens Xenoandrogens Antiestrogens Endocrine regulators in the food chain Endocrine disruptors action on mechanism of estrogen and androgen Impacts of EDCs on AR and/or ER Chromosomal abnormalities DNA damage Micro RNAs Data associated with exposure to endocrine disruptors in carcinogenesis Incidence of breast cancer due to endocrine disrupting chemicals Multiple combinations of risk components Identification of problems associated with the mode of action of EDCs Case studies of endocrine Disrupting chemicals associated with breast cancer Endocrine disrupting chemicals: Diethylstilbesterol in pregnant women Impact of endocrine disruptors on the development of cancer in women Dioxins Dichlorodiphenyltrichloroethane Methoxychlor Atrazine and triazine herbicides Chlorpyrifos and other pesticides Health issues Conclusions and future prospective References 11 Environmental exposures as xenoestrogens (bisphenol A and phthalates) enhance risk for breast cancer Introduction Risk factors as models for environmental chemicals and breast cancer Chemical properties and main sources of exposure to bisphenol A and phthalates Bisphenol A and breast cancer Government policy for bisphenol A Mechanism of bisphenol A-induced breast cancer Estrogenic potential of bisphenol A Epigenetic impacts of bisphenol A DNA damage Changes of breast microenvironment Phthalates Exposure via diet Toxicological aspects and human health effects Phthalates and breast cancer Conclusion References 12 Biotransformation of toxic xenobiotics by human gut microbiota Introduction Habitat of microbes in human body Role of microbes in health and disease Microbiome regulation of toxicity The metabolome of microbes Function of gut microbes in cellular physiology Gut microbial interactions with xenobiotics The complementary chemistry of microbial xenobiotic metabolism Metabolization of environmental chemicals by GI microbiota Metabolism of environmental chemicals by the GI microbes Polycyclic aromatic hydrocarbons Nitrated PAHs or nitro-PAHs Nitrotoluenes Pesticides Polychlorobiphenyls Effect of environmental chemicals on the activity of GI microbes Pesticides Other organic pollutants Factors affecting the rate and level of gut microbes in xenobiotic metabolism Advanced technologies for the identification of xenobiotic-degrading microbes Computational method for the prognosis of species-specific biotransformation of xenobiotic compounds by gut microbiota Methods Construction of gut bacterial substrate database Conclusion References 13 Mechanism of resistance to toxic xenobiotics in humans Introduction Cellular adaptation to xenobiotics Evolution of resistance to toxic xenobiotics Impact of xenobiotics on physiology and gene expression of human gut microbiota Cancer drug resistance Types of resistance Mechanisms of resistance to xenobiotics P-glycoproteins as universal detoxifiers Function of P-glycoprotein for resistance to carcinogenic agents Link between environmental chemicals and chemoresistance Conclusions References 14 Profiling the reactive metabolites of xenobiotics in cancer Introduction Experimental methods for the assessment of reactive metabolites Analysis of covalent binding to proteins Trapping and identifying reactive metabolites Time and cofactor-based cytochrome P450 suppression NMR spectroscopy for identification of xenobiotic toxicity High-throughput NMR in xenobiotics toxicology Characterization of xenobiotic metabolites by LC/HRMS/MS Screening of xenobiotics in by UHPLC-HRMS/MS Example for determination of unknown xenobiotic compounds Reagents Extraction of xenobiotics UHPLC-qOrbitrap Analysis Target analysis and suspect screening Profiling of seasonal variation in and cancer risk assessment of benzo(a)pyrene and heavy metals in drinking water Materials and methods Extraction and analysis of benzo(a)pyrene in water samples Enzyme-linked immunosorbent assay (ELISA) test kit method Extraction and analysis of heavy metals Cancer risk assessment Toxicological analysis of anthropogenic xenobiotics associated with environmental metabolomics Environmentally relevant organisms and anthropogenic contaminants Identification of metabolites and pathways Conclusions References 15 Toxicogenomics for the prediction of carcinogenicity of xenobiotic substances Introduction Mechanistic inference to toxicogenomics Onset of system toxicology Emergence of molecular toxicology Emergence of the field of toxicogenomics Genetic toxicology: transcriptomics Next-generation sequencing Artificial intelligence and machine learning High-throughput screening Predictive toxicology Toxicogenomics-related exploration of pathways for immunotoxicity Prediction of carcinogenicity effects of xenobiotics by toxicogenomics methods Genotoxic and nongenotoxic carcinogenesis Analysis of genotoxic carcinogenicity by toxicogenomics methods Assessment of nongenotoxic carcinogenicity by toxicogenomics methods Conclusions and future prospective References Index