Damage intracellular

Toxicity is most likely in tissues that interact with the drug. For example, gentamicin is polycationic and binds to anionic phospholipids in the cell membranes of renal proximal tubular cells, where it inhibits phospholipases and damages intracellular organelles. 

It is being recognized that an increasing number of protein toxins from bacteria and plants act on targets located in the cytosol. Recently it has been shown that such toxins can be used to carry passenger proteins across cellular membranes into the cytosol. A common feature of the toxins in question is that they consist of two functionally different parts, A and B. The B-moiety binds the toxin to cell surface receptors, a binding which is required to produce the toxic effect at low concentrations of the toxin. The A-moiety is an enzyme that enters the cytosol and damages intracellular components. The B-moiety may be a separate part of the same protein as the A-moiety, or it may consist of one or several separate polypeptides. 

The epithelium of the terminal bronchiole is the first area to be damaged. Intracellular vesiculation of both ciliated and Clara cells has been noted. This appears to be a relatively immediate effect. 

Mankind has used metals for milletmia, but the relation between metals and cancer has only been known for over a century. Only in the past tlnee decades have the tools been available to analyze the molecular and cellular effects of metals on cancer, and only very recently has it been possible to examine the role of free radicals in normal and disease states. Because of their ability to produce free radicals, transition metals provide a nnique means by which to study not only metal-related diseases, but the effects of free radicals on DNA damage, intracellular signaling, and cell-to-cell coimnunication. With the completion of the human genome project and the use of novel technologies snch as genomics and proteomics, it will soon be possible to examine the global effects of free radicals on genes and their expression. 

Experiments with radioactive streptomycin showed that there was an immediate uptake of the antibiotic by the cells and that this was followed, after a short interval, by a secondary uptake. The secondary uptake may be due to the entry of streptomycin into the cell through the defective growing membrane, and may thus enable the drug to damage intracellular enzymes. Hurwitz and Rosano have concluded that streptomycin exerts its effect in two phases and that the secondary phase, in which the antibiotic is directly lethal, is insensitive to chloramphenicol. However, an attempt to confirm the existence of a chloramphenicol insensitive phase has been unsuccessful. 

Bredinin, Neosidomycin, and SF-2140. Bredinin (62), isolated from the culture filtrates of Eupenicillium brefeldianum (1,4), inhibits the multiplication of L5178Y, HeLa S3, RK-13, mouse L-ceUs, and Chinese hamster cells. GMP can reverse the inhibition by (62), but (62) is not incorporated into the nucleic acids. The inhibition of nucleic acid synthesis and chromosomal damage in the S and G 2 phases that is caused by (62), is reversed by GMP. It blocks the conversion of IMP to XMP and XMP to GMP. In combination with GMP, (62) interferes with intracellular cAMP levels and thereby inhibits cell division. 

Costs of downstream processing for bioprocesses are increased by 1) low concentrations of products, 2) numerous impurities at low concentration and 3) intracellular materials (if cell disruption is necessary). However, the high specificity of biocatalysts is a benefit to downstream processing since products closely related to the desired product are less likely to be present Waste products of bioprocesses are likely to be less environmentally damaging, which also reduces downstream processing costs. 

The higher molecular weight organotin(IV)s, such as TBT and TFT, are known to be immunotoxic and to cause renal and hepatic damage. TBT at environmentally relevant concentrations increases intracellular concentration of Ca(II) ([Ca(II)],) in murine thymocytes by increasing membrane Ca(II) permeability and... 

In both plant (e.g. [57]) and animal (e.g. [86]) cell systems, cellular respiration has been shown to be a more sensitive indicator of system response to hydro-dynamic stress than membrane integrity, suggesting that intracellular enzymes and/or organelles may be affected at stress levels lower than those required to cause membrane damage. 

Another condition due to mutations in the RYRl gene is central core disease. This is a rare myopathy presenting in infancy with hypotonia and proximal muscle weakness. Electron microscopy reveals an absence of mitochondria in the center of many type I (see below) muscle fibers. Damage to mitochondria induced by high intracellular levels of Ca secondary to abnormal functioning of RYRl appears to be responsible for the morphologic findings. 

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