Non-specific cytotoxic cells

Jaso-Friedmann, L., J.H. Leary, III and D.L. Evans. The non-specific cytotoxic cell receptor (NCCRP-1) molecular organization and signaling properties. Dev. Comp. Immunol. 25 701—712, 2001. 

NCC non-specific cytotoxic cells TBHQ tert-butylhydroquinone... 

T lymphocytes, thymus-derived lymphocytes or T cells are formed in the thymus. They carry out immune reactions involving cell-cell interactions and are responsible for cell-mediated immunity. One distinguishes specific and non-specific cytotoxic killer T cells, (NK cells, natural killer cells), and helper T cells which cooperate with antigen-presenting cells, APC s, in the initiation of an immune response. Suppressor T cells dampen the action of helper T cells. 

Inorganic mercury salts have a half-life in the body of about 40 days. Mercury binds to a wide range of enzyme systems and has a particular affinity for proteins containing sulphydryl (-SH) groups. As these are widespread, mercury may bind to microsomes and mitochondria, producing a non-specific cytotoxicity and cell death. In the kidney, mercuric mercury induces synthesis of metallothionein, a metal-binding protein, and is foimd localised in lyosomes. 

As stated above, it is of crucial importance to distinguish specific antiprotozoal effects from non-specific cytotoxicity. It is certainly possible to do so for individual compounds, e.g. by calculating the ratio of IC50 values for antiprotozoal and for cytotoxic activity as was done e.g. in [77, 78], On the other hand, it has been demonstrated that cytotoxicity data for STLs vs. different cell lines do not necessarily... 

Based on these considerations, there is substantial merit associated with an approach that relies on selective cytotoxicity. Paradoxically, however, all of the well-known natural product antitumor agents that are currently utilized in clinical settings do not demonstrate selective cytotoxicity (2). Rather, it is typical to observe a general cytotoxic response with absolutely no cell-type specificity. Since it is not practical to assign a high priority to a plant extract based solely on non-specific cytotoxic activity, it is necessary to devise a broader-based bioassay-directed drug discovery program. 

Siccayne (139) displayed a non-specific cytotoxicity by interfering with the uptake of nucleoside precursors into eucaryotic cells as well as with the in vitro incorporation of nucleotides into DNA and RNA [141]. 

Another reason for complexity of cell-activation mechanisms resides in the end response of neutrophils - that is, the delivery of cytotoxic products. Whilst these products are highly lethal towards pathogens, they can also attack and destroy host tissues, and this can have deleterious effects on tissue function. Complex intracellular signalling mechanisms to activate these cytotoxic pathways also guards against non-specific activation, which could lead to host tissue damage. 

For anti-tumour drugs, Ozawa et cd. [27] proposed the following models. For cell cycle phase non-specific drugs (type I drug), the cytotoxic activity depends on the drug exposure, as reflected in the area under the intracellular concentration-time profile (AUC), and can be modelled using the following formula [2,28] ... 

Hydrogen peroxide transformed mouse myeloid progenitor cells (FDC-Pl) from interleukin-3 dependence to factor independence, but only at cytotoxic concentrations (> 12/5 pmol/L). Such a transformation was not induced by non-specific insults to the cells, such as sodium fluoride or heat shock treatment. The transformed cells produced tumours when injected into pre-irradiated mice (Crawford Greenberger, 1991). Hydrogen peroxide (10 pmol/L) induced overexpression of the proto-oncogene c-jun in hamster tracheal epithelial (HTE) cells c-jun overexpression led to proliferation and increased growth rate, as well as increased anchorage-independence of HTE cells (Timblin et al., 1995). 

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