Cell toxicity

To ensure that the inhibition of EGF binding by palytoxin was not a consequence of cell toxicity, the effect of palytoxin on DNA synthesis in Swiss 3T3 cells was monitored. When cells were incubated in the presence of palytoxin, 10% fetal calf serum, and H-thymidine for 19.5 hr, no depression in the extent of H-thymidine incorporation into DNA was detected up to 3.7 pM palytoxin (Table I). Although 11 pM palytoxin was toxic when present for a prolonged period, under the conditions of the assays described above no toxicity was detected (Table I). When cells were incubated in the presence of palytoxin, 0.1% fetal calf serum, and H-thymidine, palytoxin did not stimulate significant incorporation of H-thymidine into DNA. Thus, although it can modulate the EGF receptor system under these conditions, palytoxin alone does not appear to be mitogenic for Swiss 3T3 cells. 

Pyrene is metabolized by the fungus Crinipellis stipitaria to 1-hydroxypyrene, and this has a spectrum of toxic effects substantially greater than those of pyrene these include cytotoxicity to HeLa S3 cells, toxicity to a number of bacteria and to the nematode Cae-norhabditis elegans (Lambert et al. 1995). 

Mossman, B.T. and Marsh, J.P. (1985). Mechanisms of cell toxic injury by asbestos fibres role of oxygen free radicals. In In vitro Effects of Mineral Dusts (eds. E.G. Beck and J. Bignon) pp. 66-81. Springer Verlag, Berlin. 

Chmura SJ, Dolan ME, Cha A, Mauceri HJ, Kufe DW, Weichselbaum RR. In vitro and in vivo activity of protein kinase C inhibitor chelerythrine chlorise induces tumor cell toxicity and growth delay in vivo. Clin Cancer Res 2000 6 737-742. 

However, in order to avoid the epoxide moiety in 4-67, which might serve as a locus of nondiscrimimating cell toxicity, these authors focused their activity on the cyclopropane-analogue 4-70 by heating a mixture of 4-68 and 4-69, which led to 4-70 with extrusion of isobutene in 75% yield (Scheme 4.15). 

While the use of FRET probes in vitro is inflicted with a limited number of complications, the use in biological samples or in living cells needs much more careful considerations since factors such as enzyme specificity, cell toxicity, and spatio-temporal resolution usually play an important role. 

Heydenreich, A.V., Westmeier, R., Pedersen, N., Poulsen, H.S., and Kristensen, H.G., Preparation and purification of cationic solid lipid nanospheres effects on particle size, physical stability and cell toxicity, International Journal of Pharmaceutics, 2003, 254, 83-87. 

Complement-mediated cell toxicity, attraction of macrophages, inhibition of function, etc. 

The effects of raloxifene on bone histomorphometry were analyzed by Ott et al. (2002). In a group of 54 women enrolled in the MORE study, two transiliac bone biopsies were obtained at baseline and after 2 years of treatment. The results confirmed the safety of the drug on bone tissue since no woven bone, mineralization defect, cell toxicity, or medullary fibrosis was observed. Moreover, the number of empty osteocytic lacunae also suggested an antiapoptotic effect on the osteocyte. More recent experimental data further confirm this antiapoptotic effect of raloxifene on osteoblastic and osteocytic cells (Taranta et al. 2002). 

Rosenthal, D.S., et al., Mechanisms of JP-8 jet fuel cell toxicity B. Induction of necrosis in skin fibroblasts and keratinocytes and modulation of levels of Bcl-2 family members, Toxicol. Appl. Pharmacol., 171, 107, 2001. 

Oral or parenteral administration of mercuric chloride promotes lipid peroxidation [127-129], possibly via a reduction of glutathione peroxidase activity. However, several studies argue against lipid peroxidation being responsible, at least for the early hours of cell toxicity of mercury [130-133]. 

Looked at another way, the four major carcinogenic mechanisms are DNA damage, cell toxicity, cell proliferation and oncogene activation. Any effective program to identify those drags which have the potential to cause or increase the incidence of neoplasia in humans must effectively screen for these mechanisms (Kitchin, 1999). 

Bracher, M., Faller, C., Spengler, J. and Reinhardt, C.A. (1987). Comparison of in vitro cell toxicity with in vivo eye irritation. Molec. Toxicol. 1 561-570. 

Misonidazole [27 l-methoxy-3-(2-nitroimidazol-l-yl)-2-propanol] and the model compound l-methyl-2-nitroimidazole have been used as radiosensitizers in the treatment of certain types of human tumors. One important property of these compounds is that they are more toxic to hypoxic cells than to aerobic cells, indicating that reductive metabolism of the drug is involved in the toxicity. Results of a number of studies suggest that intracellular thiols play a significant role in the hypoxic cell toxicity, and it was found that reduction products formed stable thio ethers with GSH (for literature see References 181-183). The reaction mechanism of thio ether formation has not been fully established. It has been suggested that the 4-electron reduction product was involved in thio ether formation181,184,185, and that the hydroxylamine rather than the nitroso derivative was the reactant. On the other hand, an intermediate nitroso derivative is expected to give a sulfenamide cation (see Scheme 1) which easily allows thio ether formation. 

Keywords analytical electron microscopy, carbon nanoparticles, macrophage cell, toxicity... 

Plewa MJ, Wagner ED, Muellner MG, Hsu KM, Richardson SD (2008) Comparative mammalian cell toxicity of N-DBPs and C-DBPs. In Karanfil T, Krasner SW, Westerhoff P, Xie Y (eds) Occurrence, formation, health effects and control of disinfection by-products in drinking water, vol 995. American Chemical Society, Washington DC, pp 36-50... 

Richardson SD, Fasano F, Ellington JJ, Crumley FG, Buettner KM, Evans JJ, Blount BC, Silva LK, Waite TJ, Luther GW, McKague AB, Miltner RJ, Wagner ED, Plewa MJ (2008) Occurrence and mammalian cell toxicity of iodinated disinfection byproducts in drinking water. Environ Sci Technol 42 8330-8338... 

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