Cuvette and flow system for fast and sensitive spectrophotometric assays of oxygen consumption.
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Biomedical subjects
Publications and source records attributed to A Bara.
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The Crabtree effect can be observed when the O2 consumption of tumour cells or of mammalian cells grown in culture is measured in physiological medium containing glucose. The effect of 2 hypoxic cell radiosensitizers, misonidazole and NDPP, on the O2 consumption of Ehrlich ascites tumour cells was compared in media with and without glucose. A stimulatory effect on O2 consumption was found for 5--20mM misonidazole as well as for 0.5mM NDPP, both in media containing 10(-2)M glucose. Thus glucose induced a Crabtree effect in Ehrlich tumour cells, expressed as 38--45% inhibition of O2 consumption relative to that in the same medium without glucose. The stimulatory effect of misonidazole and NDPP on O2 utilization in medium with glucose undoubtedly appeared as a release from the Crabtree effect.
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Misonidazole increased oxygen consumption of Ehrlich ascites cells and reversed the blockage of oxidative phosphorylation induced by amytal and KCN. It alos increased oxygen consumption of mitochondria in the presence of alpha-ketoglutarate substrate, but decreased the respiratory control ratio. Cellular oxygen consumption decreased, but mitochondrial consumption was increased by metronidazole, and the respiratory control ratio was not affected by this substance. It was concluded that misonidazole influences respiration in a similar way to uncouplers, and the interaction site for both substances is at the NADH level. These respiratory effects can be of importance in altering radiation response in multicellular tissues.
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(Diphenylphosphinodithioato) diphenylantimony (III), Ph2SbS2PPh2 (1) and (diisopropylphosphorodithioato) diphenylantimony(III), Ph2SbS2P(OPri)2 (2) were tested in vivo in male AKR mice and in vitro against Ehrlich ascites tumor cells. Both compounds exhibited dose-dependent inhibitory effects on in vivo tumor growth and on in vitro cell proliferation, cell viability, respiration and protein synthesis. The activities of some enzymes involved in energetic metabolism (Ca-ATPase, LDH, G6Pase) were exacerbated in vitro. The inhibitory effects could be related to the imbalance between ATP-producing and ATP-consuming processes in Ehrlich ascites tumor cells and also to their cell-cycle specificities.
Diphenyltin(IV) and diphenylantimony(III) derivatives of dithiophosphorus ligands, i.e. Ph2Sn(S2PPh2)2 (1), Ph2Sn[S2P(OPr)2]2 (2), Ph2SbS2PPh2 (3) and Ph2SbS2P(OPri)2 (4), have been tested in vitro and in vivo against Ehrlich ascites tumor. All four compounds were almost equally effective in vitro, exhibiting inhibitory effects on cell proliferation, viability and protein synthesis, and exacerbated respiration and Ca-ATPase activity. In mice bearing Ehrlich ascites tumor cells, all four compounds inhibited the tumor growth, the organometallic phosphorodithioates being more active than phosphinodithioate analogues, and the organoantimony derivatives more active than organotins. Compound 4 (5 mg/kg/day, i.p., on days 1,3 and 5) produced an increase in life span of 83% and a cure rate of 30% in mice bearing this tumor.
Two organoantimony (III) derivatives, i.e., diphenylantimony diphenyl-dithiophosphinate, Ph2SbS2PPh2, and diphenylantimony diizopropyldithiophosphate, Ph2SbS2P(OPri)2, were shown to exhibit antitumor properties. Both compounds produced strong tumor inhibition effects in mice bearing Ehrlich ascites tumor. Moreover, the dithiophosphate (15 mg/kg, i.p., in days 1, 3 and 5) produced a cure rate of 30%.