Cell killing

The outcome of rapid radiation chemical processes in mammalian cells is to cause a variety of longer-Hved physical alterations in the DNA. Of these, double-strand breaks (DSBs) appear to be most frequently involved in cell killing if not correctly repaired. In general, thiols protect against DSB induction in proportion to their effect on cell killing (7), although there are exceptions (8). 

On the other hand, cNOS is continuously expressed in the ceils, and upon stimulation of the cell, the formation of NO begins immediately. However, the amounts of NO produced are minute. The nature of NO in cells expressing cNOS is only to act as a messenger molecule, whereas NO has also other functions in cells expressing iNOS. For example, NO has bacteria and cell killing properties in immunological cells, such as phagocytes. ... 

Figure 55-1. Cell kill theory describing activity of repeated chemotherapy regimens.

Gustafson KR, Cardellina JH 2nd, McMahon JB, Gnlakowski RJ, Ishitoya J, Szallasi Z, Lewin NE, Blumberg PM, Weislow OS, Bentler JA et al. A nonpromoting phorbol from the samoan medicinal plant Homalanthus nutans inhibits cell killing by mW-l.J Med Chem 1992 35 1978-86. 

Brenneman DE, Westbrook GL, Fitzgerald SP, Ennist DL, Elkins KL, Ruff MR, Pert CB (1988) Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide. Nature 335(6191) 639-642... 

Mello-Filho, A.C., Hofiman, R.E. and Meneghini, R. (1984). Cell killing and DNA damage by hydrogen peroxide are mediated bv intracellular iron. Biochem. J. 218, 273-276. 

Role of calcium in toxic cell killing. TIPS. 10, 281-285. 

The above studies have generated a huge body of invaluable data concerning the effects of oxidative stress on cells. In particular the importance of GSH in cell protection and the role of disturbed calcium homeostasis in cell killing have been greatly illuminated. 

Ortenius, S., McConkey, D.J., Bellomo, G. and Nicotera, P. (1989). Role of calcium in toxic cell killing. Trends Pharmacol. Sci. 10, 281-285. 

Once an initial remission is achieved, further intensive therapy is imperative to prevent relapse. Induction therapy fails to provide adequate cell kill, and leukemia cells survive the initial... 

In HSCT, very high doses of chemotherapy with or without total-body radiation (TBI) are given in an attempt to potentiate leukemia cell kill. Hematopoiesis is restored by the infusion of stem cells harvested from an HLA-compatible donor, thereby rescuing the patient from the consequences of total aplasia.13 It is the most effective antileukemic therapy currently available. 

Bernard, P., and Couturier, M. (1992). Cell killing by the F plasmid CcdB protein involves poisoning ofDNA-topoisomerase II complexes. J. Mol. Biol. 226, 735-745. 

Many aspects of DNA replication in filamentous phages are similar to that of < >X 174. The unique property, release without cell killing, can be briefly discussed. The release from the cell occurs by a budding process in which the virus particle is always released from the cell with the end containing the A protein first. Interestingly, the orientation of the virus particle across the cell membrane is the same for its entry and exit from the cell. There is no accumulation of intracellular virus particles the assembly of mature virus particles occurs on the inner cell membrane and virus assembly is coupled with the budding process. 

Wright, K.A., Weidman, E. and Hong, H. (1987) The distribution of cells killed by Trichinella spiralis in the mucosal epithelium of two strains of mice. Journal of Parasitology 73, 935-939. 

Suss, G. and Shortman, K. (1996) A subclass of dendritic cells kills CD4 T cells via Fas/Fas-ligand-induced apoptosis. Journal of Experimental Medicine 183, 1789-1796. 

Amongst the synthetic magnesium(II) complexes, a comparison of bis(pyridine)magnesium(II)-tetrabenzoporphyrin (26) with bis(pyridine)magnesium(II)-octamethyltetrabenzoporphyrin (10) in vitro (HeLa cells), and in vivo using liposomal delivery, showed that while (26) was more effective than (10) in cell kill, (10) had the greater tumor selectivity ([tumor]/[muscle] = 36.0 after 24 h). Zinc(II) tetrabenzoporphyrin also showed promising activity nickel(II) tetrabenzoporphyrin derivatives were inactive.117... 

In spite of the heavy atom, compound (32) is sufficiently fluorescent for this to be used as an analytical tool to examine localization and pharmacokinetics. In EMT-6 murine tumors, (32) localizes initially on lysosomes, with selectivity for tumor over surrounding normal tissue, and with evidence for apoptotic cell kill.137 Fluorescence studies using a hamster cheek pouch model show a maximum emission in 2-3 h, with selectivity for the tumor (x 1.5 over normal tissue) after 24 h the photosensitizer is no longer detectable.138 Lutetium texaphyrin (32) has been compared... 

Edwards et al. (1980) used a Cm-242 source to irradiate externally a thin film of blood. The energy of 4 9 MeV of the alpha particles were almost entirely absorbed by the blood. The dicentrics yield was linear from 0.11 to 4 2 Gy. From this resulted a RBE of 17.9 with respect to Co-60 gamma rays. It was, however, only 6.0 at the initial slope. To explain this RBE, which was low compared to that expected from neutron experiments, a model is presented taking into account cell killing and mitotic delay. 

Colloidal gold-labeled (strept)avidin can be used as highly sensitive detection reagents for microscopy techniques (Cubie and Norval, 1989) (Chapter 24). Finally, cytotoxic substances coupled to (strept)avidin can be used to direct cell-killing activity toward a tumor-cell-bound, biotinylated monoclonal antibody (or other targeting molecule) for cancer therapy (Hashimoto et al, 1984) (Chapter 21). 

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