Cellular macromolecule

Nitric oxide may induce deleterious effects when airway epithelial or immunological cells are exposed to mineral particles (asbestos, quartz). These particles also stimulate cells to produce NO in large quantities, but pulmonary cells are unable to destroy these particles, and a non-physiologically excess production of NO results, perhaps causing tissue damage due to a reaction of NO with cellular macromolecules. 

A xenobiotic is said to be stored when it is not available to sites of metabolism or action and is not available for excretion. In other words, it is held in an inert position from a toxicological point of view, where it is not able to express toxic action or to be acted upon by enzymes. A xenobiotic is stored when it is located in a fat depot (adipose tissue), bound to an inert protein or other cellular macromolecule, or simply held in a membrane that does not have any toxicological function (i.e., it does not contain or represent a site of toxic action, neither does it contain enzymes that can degrade the xenobiotic). 

Studies using radioactivity-labeled acrylonitrile indicate that acrylonitrile or its metabolites form covalent adducts with cellular macromolecules in most tissues. Studies to develop chemical or immunological methods for measuring these adducts would be especially valuable in detecting and perhaps even quantifying human exposure to acrylonitrile. Adverse health effects demonstrated following exposure to acrylonitrile, particularly acute exposures, were characteristic of cyanide toxicity. Because these effects are also indicative of exposure to many other toxicants, additional methods are needed for more specific biomarkers of effects of acrylonitrile exposure. 

Covalent binding of chemical carcinogens to cellular macromolecules, DNA, RNA and protein, is wel1-accepted to be the first step in the tumor initiation process ( 1, 2). Most carcinogens, including polycyclic aromatic hydrocarbons (PAH), require metabolic activation to produce the ultimate electrophilic species which react with cellular macromolecules. Understanding the mechanisms of activation and the enzymes which catalyze them is critical to elucidating the tumor initiation process. 

From knowledge presently available, the ability of PAH to bind covalently to cellular macromolecules appears to depend mainly on two factors the ease of formation of PAH radical cations, which is measured by their IP, and localization of positive charge in the radical cation. The IP of numerous PAH have been determined and compared to a qualitative measure of their carcinogenicity (16). 

Although metabolically-formed N-sulfonyloxy arylamides are strong electrophiles, bind to cellular macromolecules, and have long been considered ultimate carcinogens, their precise role in aryl-... 

A major consequence of oxidative stress is damage to cellular macromolecules. Addition of a free radical... 

Conversion of epoxides (arene oxides) into phenols is spontaneous. The conversion of epoxides into dihydrodiols is catalyzed by EH (EC 4.2.1.63). Hydroxyl containing PAHs can act as substrates for conjugases (C) (UDP glucuronsyl transferase (EC 2.4.1.17) and phenol sulphotransferase (EC 2.8.2.1)). This pathway usually leads to inactive excretable products. Epoxides are scavenged by GSH and the reaction is catalyzed by GSHt (EC 2.5.1.18). When GSH is depleted and/or the other pathways are saturated, epoxides of dihydrodiols (particularly 7,8-diol-9,10-epoxides in the case of BP) and phenol metabolites react with cellular macromolecules such as DNA, RNA, and protein. If repair mechanisms are exceeded the detrimental effects of PAH may result. 

The first step in all RNA isolation protocols involves lysing the cell in a chemical environment that denatures ribonucleases. The RNA is then fractionated from other cellular macromolecules by either homogenizing the tissue (dissected brain tissue) or simply vortexing the sample (very small tissues and laser-microdissected sample) without further homogenization. The cell type from which the RNA is to be isolated, the sample size, and the eventual use of the RNA will determine which procedure described here is appropriate. 

The mechanism of benzene-induced toxicity appears to involve the concerted action of several benzene metabolites. Benzene is metabolized, primarily in the liver, to a variety of hydroxylated and opened-ring products that are transported to the bone marrow, where secondary metabolism occurs. Metabolites may induce toxicity both by covalent binding to cellular macromolecules and by inducing oxidative damage. Metabolites may also inhibit stromal cells, which are necessary to support growth of differentiating and maturing marrow cells. ... 

Since biological systems are rich in nucleophiles (DNA, proteins, etc.) the possibility that electrophilic metabolites may become irreversibly bound to cellular macromolecules exists. Electrophiles and nucleophiles are classified as hard or soft depending on the electron density, with hard electrophiles generally having more intense charge localization than soft electrophiles in which the charge is more diffuse. Hard electrophiles tend to react preferentially with hard nucleophiles and soft electrophiles with soft nucleophiles. 

The process of drug interaction with cellular macromolecules (receptors) to alter physiological function (i.e., receptor theory)... 

Cytotoxic and immunosuppressive drugs, which inhibit the synthesis or action of crucial cellular macromolecules, such as nucleic acids, are used in three broad categories of skin disease hyperproUferative disorders, such as psoriasis immunological disorders, such as autoimmune bullous diseases and skin neoplasms. The pharmacology of these drugs is discussed in Chapter 57. 

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