Authors
Published in Comprehensive Toxicology
Mechanisms of Tumor Progression
Published in Comprehensive Toxicology
Tumor progression is a term widely used in reference to phenotypic changes in an already-formed neoplastic lesion. It is a complex phenomenon characterized by well-defined morphological, molecular, and functional changes in tumor cells and encompasses a wide variety of mechanisms. This chapter discusses tumor progression as a mutation and selection...
Xanthine Oxidoreductase and Aldehyde Oxidase *
Published in Comprehensive Toxicology
Aldehyde oxidase (AO) and xanthine oxidoreductase (XOR) are closely related enzymes with very similar primary structures comprising two identical subunits each of which contains four redox centers: one molybdopterin cofactor, one flavin adenine dinucleotide (oxidized form) (FAD) molecule, and two iron–sulfur clusters. The enzymes, also referred to ...
Receptor-Mediated Carcinogenesis
Published in Comprehensive Toxicology
A variety of xenobiotics such as dioxin, peroxisome proliferators, hormones, and phorbol esters result in tumors without directly damaging DNA. Instead, these compounds are classified as tumor promoters and their mode of action includes affecting cellular proliferation, apoptosis, or differentiation. The manner in which the aforementioned chemicals...
Glutathione Peroxidases
Published in Comprehensive Toxicology
Seven glutathione peroxidase (Gpx) genes have been identified in the human and mouse genomes. The conserved redox-active amino acid residue is selenocysteine in most of the enzymes and cysteine in the others. The Gpxs vary in their reaction characteristics and distribution within the organism. Gpx1 is the most abundant and widely distributed Gpx. I...
Organochlorine and Pyrethroid Insecticides *
Published in Comprehensive Toxicology
The synthesis of dichlorodiphenyltrichloroethane (DDT) by Zeidler in 1874 marked the beginning of a new era characterized by the large-scale utilization of synthetic chemicals to control various pests and pest-borne diseases. The success of DDT quickly led to the introduction of other chlorinated hydrocarbons including lindane, aldrin, dieldrin, en...
Olfactory System
Published in Comprehensive Toxicology
The nose has several critical functions including conditioning inhaled air and olfaction. The nasal passage is lined by olfactory, respiratory, squamous, transitional, and lymphoepithelial epithelium. Each nasal epithelium may be subject to toxicant-induced injury. Toxicant-induced epithelial lesions in the nasal passages are often site-specific an...
Behavioral Screening for Toxicology
Published in Comprehensive Toxicology
Screening for behavioral toxicity, or neurotoxicity, has been in use for decades; however, only in the past 20 years has this become a standard practice in toxicology. Current screening batteries, such as the functional observational battery (FOB), are derived from protocols used in pharmacology, toxicology, and psychology. Although there is a rang...
Environmental Endocrine Disruptors and Male Reproductive Toxicology
Published in Comprehensive Toxicology
Many natural and synthetic chemicals can alter endocrine signaling by mimicking or inhibiting the actions of endogenous hormones. These chemicals, now commonly referred to as endocrine disruptors or endocrine disrupting chemicals (EDCs), can alter male reproductive tract development and function by effects on the estrogen, androgen, thyroid hormone...
Modifications of Mitochondrial Function by Toxicants
Published in Comprehensive Toxicology
Mitochondria are membrane-enclosed organelles regarded as ‘cell power plants.’ Mitochondria generate most of the ATP in cells via ATPase rotation driven by the proton flow across the inner membrane by a process called chemiosmosis. This generates electrical potential energy in the form of a pH gradient across this membrane. The energy is released a...
