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Advances in Molecular Toxicology

Author : James C. Fishbein
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Advances in Molecular Toxicology

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Advances in Molecular Toxicology features the latest advances in all of the subspecialties of the broad area of molecular toxicology. Toxicology is the study of poisons and this series details the study of the molecular basis by which a vast array of agents encountered in the human environment and produced by the human body itself manifest themselves as toxins. Not strictly limited to documenting these examples the series is also concerned with the complex web of chemical and biological events that give rise to toxin-induced symptoms and disease. The new technologies that are being harnessed to analyze and understand these events will also be reviewed by leading workers in the field. Advances in Molecular Toxicology will report progress in all aspects of these rapidly evolving molecular aspects of toxicology with a view toward detailed elucidation of both progress on the molecular level and on advances in technological approaches employed. * Cutting edge reviews by leading workers in the discipline. * In depth dissection of molecular aspects of interest to a broad range of scientists, physisicans and any student in the allied disciplines. * Leading edge applications of technological innovations in the chemistry, biochemistry and molecular medicine.

Advances in Molecular Toxicology

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Advances in Molecular Toxicology, Volume 11, features the latest advances in the subspecialties of the broad area of molecular toxicology. This series details the study of the molecular basis of toxicology by which a vast array of agents encountered in the human environment, and produced by the human body, manifest themselves as toxins. The book is not strictly limited to documenting these examples, but also covers the complex web of chemical and biological events that give rise to toxin-induced symptoms and disease. The new technologies that are being harnessed to analyze and understand these events are also reviewed by leading experts in the field. Provides cutting-edge reviews by leading workers in the discipline Includes in-depth dissection of the molecular aspects that are of interest to a broad range of scientists, physicians and any student in the allied disciplines Presents leading-edge applications of technological innovations in chemistry, biochemistry and molecular medicine

Molecular Toxicology

Author : P. David Josephy
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The science of toxicology has progressed considerably since Molecular Toxicology was first published in 1997. New advances in biochemical and molecular biological experimental techniques have helped researchers understand the precise effects of toxins and foreign compounds on living things at the molecular, cellular, and organismal levels. Breakthrough research has recently been completed illuminating the human genome and the role of enzymes in toxic biochemical reaction mechanisms. Toxicology now covers drug metabolism and design, carcinogenesis, programmed cell death, and DNA repair, among other subjects. The second edition captures these and other advances, and broadens its scope to address the experimental science of toxicology. The first edition of Molecular Toxicology has become an indispensable resource for graduate students in molecular and biochemical toxicology courses, as well as academic researchers and industrial researchers in toxicology. Rigorously updated and revised, the new edition commands an unrivaled authority in the field of molecular toxicology.

Advances in Molecular Toxicology

Author : Umeo Takahama
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Salivary nitrate derived from foods is reduced to nitrite and nitric oxide (NO•) by oral bacteria. NO• is transformed into NO2•, N2O3, and ONOOH by chemical reactions, and nitrite is oxidized to NO2• by salivary peroxidase. The formation of reactive nitrogen oxides becomes faster with the decrease in pH of dental plaque from 7 to 5. Reactive nitrogen oxides formed in acidified plaque can activate leukocytes through oxidation, nitration, and nitrosation of free and bacterial proteins in plaque and the gingival crevice. O2•− and NO• produced by activated leukocytes can contribute to stresses to the gingival tissues. This chapter deals with mechanisms of production of reactive nitrogen oxides in the oral cavity, especially, acidified plaque. Since salivary nitrite is transported to the stomach, this chapter also deals with reactions of salivary nitrite in the stomach.

British Toxicology Society Annual Congress Spring 2008

Author : Matthew C. Wright
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Advances in Molecular Toxicology

Author : Sigeng Chen
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Organophosphate (OP) exposure continues to be a threat to both civilian and military personnel. Sensitive and specific methods for the detection and remediation are needed not only for public health but also for farmers who are exposed to OPs frequently. Although detection approaches based on a mass spectrometry are sensitive and reliable, they require expensive equipment and expert operators. In addition, instrumentation such as mass spectrometer cannot be easily deployed in the field. Attempts to make point-of-care approaches have been the trend in both detecting and rescuing OP exposure in the current research of OP toxicity. This chapter will discuss some recent progress reported concerning the immunodetection of OP exposure and improved antidote therapy in the remediation of OP exposure.

Advances in Molecular Toxicology

Author : Oksana Lockridge
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The acute toxicity of organophosphorus (OP) nerve agents and pesticides is due to inhibition of acetylcholinesterase (AChE) activity in cholinergic nerve synapses. Delayed neuropathy involves OP binding to neuropathy target esterase (NTE) in neurons. AChE and NTE are serine hydrolases. In vitro studies have demonstrated that OP toxicants bind not only to serine hydrolases but also to proteins that have no active site serine, for example, Tyr 411 of human albumin and Lys 296 of mouse transferrin. Mice treated with low doses of chlorpyrifos have OP-modified tubulin in brain. Mass spectrometry has identified OP-modified albumin in the blood of humans self-poisoned by chlorpyrifos and dichlorvos. Albumin is weakly reactive with OP, but the presence of OP-modified albumin in humans suggests the existence of additional noncholinesterase OP targets. In conclusion, long-term adverse effects from OP exposure may involve OP modification of proteins that have no active site serine.

Advances in Molecular Toxicology

Author : Jason Matthews
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The aryl hydrocarbon receptor (AHR) and estrogen receptors (ERs) are ligand-activated transcription factors and members of the basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) and nuclear receptor (NR) superfamilies, respectively. The bHLH-PAS and NRs regulate many vital physiological processes including metabolism, circadian rhythm, differentiation, development, and reproduction. However, both receptor families are also associated with numerous human diseases. Reciprocal crosstalk between AHR and ERs is proposed to both positively and negatively impact human health. ERs are the most important targets in the treatment of breast cancer. The AHR, which is activated by many environmental pollutants, natural/dietary compounds, and endogenous substances, is a negative regulator of ER function. The role of ERα in AHR signaling is less clear as it is known to exhibit cell-type and promoter-specific differences. In this chapter, we will highlight the current understanding of AHR and ER crosstalk and toxicity.

Advances in Molecular Toxicology

Author : Arno G. Siraki
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Aromatic amines (also known as arylamines) form a very important class of xenobiotics. The arylamine substructure is found in pesticides, carcinogens, and drugs. It is therefore unsurprising that arylamine drugs possess varying degrees of toxicity which ultimately depend on dose, exposure, and the particular genetic makeup of the individual. Arylamines have been shown to undergo oxidation reactions to produce reactive metabolites. This chapter will focus on a subset of reactive metabolites which are the arylamine-free radical metabolites. A detailed discussion on how these free radical metabolites form is presented, and association between the latter and toxicity reactions are discussed. Particular emphasis is devoted to the subject of arylamine-induced blood dyscrasias and recent advances as well as future prospects in this area.