Increased DNA chain breakage by combined action of bleomycin and superoxide radical

The effect of quindoxin on the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid, and protein in Escherichia coli KL 399 was examined under aerobic and anaerobic conditions. In the absence of oxygen the synthesis of DNA was completely inhibited by 10 ppm of quindoxin, whereas the syntheses of ribonucleic acid and protein were not affected. Quinoxalin-di-N-oxides (QdNO) induce degradation of DNA in both proliferating and non-proliferating cells.polA, recA, recB, recC, exrA, and uvrA mutants were more susceptible than the corresponding repair-proficient strains. All strains were more resistant in the presence of oxygen. The potent in vivo activity of various quinoxaline-1,4-di-N-oxides (QdNO) against diverse bacteria, Entamoeba histolytica, and Chlamydiae of the psittacosis-lymphogranuloma venereum group has been known for more than two decades (9,24,29,35,50). Like many antibiotics (e.g., penicillin or tetracyclines) and chemotherapeutics (e.g., nitrofuran or sulfonamide), QdNO increase the live weight gain in young chickens, pigs, and calves when added to the diet (5,12,16,37). At present two QdNO, carbadox and olaquindox, are on the market as growth promoters in various countries; a third, quindoxin, has been withdrawn.QdNO were first prepared as potential antagonists of vitamin K activity, but such antagonism has never been demonstrated (24,35). Only a few further reports on the mode of action have been published. Studies on the effect of 2,3-dihydroximethyl-quinoxaline-1,4-di-N-oxide on the incorporation of radioactive precursors into deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein in Escherichia coli revealed a specific inhibition of DNA synthesis (15). Morphological changes in cells of E. coli and Staphylococcus aureus treated with 2,3-dihydroxit Present address:

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“…Furthermore, the activation of streptonigrin, bleomycin, and phleomycin is stimulated by the presence of oxygen (25,43,48).…”

Section: Resultsmentioning

confidence: 99%

Mode of Action of Quindoxin and Substituted Quinoxaline-di- N -Oxides on Escherichia coli

Suter

Rosselet

Knüsel

1978

Antimicrob Agents Chemother

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“…Whereas the superoxide molecule enhances bleomycin-induced DNA damage, SOD inhibits the process (22). SOD has been shown in vivo to reduce x-ray-induced toxicity (4) and in cell culture to inhibit the clastogenic effects of TPA (23), a free-radical producer (8).…”

Section: Resultsmentioning

confidence: 99%

Modifiers of free radicals inhibit in vitro the oncogenic actions of x-rays, bleomycin, and the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.

Borek¹,

Troll²

1983

Proc. Natl. Acad. Sci. U.S.A.

100

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Using short-term cultures of hamster embryo cells, we have examined the effects of the free-radical scavenger superoxide dismutase (superoxide: superoxide oxidoreductase, EC 1. 15. 1. 1) and the enzyme catalase (hydrogen-peroxide:hydrogenperoxide oxidoreductase, EC 1.11.1.6) on x-ray-and bleomycin-induced transformation and on the enhancement of radiogenic transformation by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). We find that superoxide dismutase inhibits (i) transformation induced by x-ray and bleomycin and (ii) promotional action of TPA in vitroa The results suggest that the oncogenic action of x-rays and bleomycin and the enhancement of oncogenic transformation by TPA are mediated in part by free radicals. The findings also suggest that superoxide dismutase can serve as an inhibitor of oncogenesis and that its actions, as seen in this in vitro system, are most predominantly on inhibiting late events in the progression of cellular transformation-those associated with promotion.

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“…Another consequence of leaky lysosomes and cellular acidification is the reactivation of DNase II, which is usually inhibited in cancer cells (Daoust and Amano, 1963;Taper, 1967Taper, , 1980Taper et al, 1971Taper et al, , 1981. H 2 O 2 and ROS can also alter nucleosides, inhibit DNA synthesis, induce DNA strand breaks, and inhibit DNA repair (Ishida and Takahashi, 1975;Morgan et al, 1976;Lesko et al, 1980;Bram and Fridovich, 1981;Lupulescu, 1991;Menon et al, 1998). Together, these actions explain the decreased Feulgen staining in VCtreated cells (Figs.…”

Section: Cytotoxicity Of Ascorbatementioning

confidence: 99%

Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment

Gilloteaux¹,

Jamison²,

Arnold³

et al. 2005

Anat. Rec.

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Feulgen and actin-phalloidin staining as well as gel electrophoresis have been employed in conjunction with cell ultrastructure to describe the effects of 1-, 2-, and 4-hr ascorbate (VC), menadione (VK 3 ), and ascorbate:menadione (VC:VK 3 ) treatments on the T24 human bladder carcinoma cell line. T24 cells exposed to VC alone display blebs and other superficial membrane defects related to membrane alterations and to superficial cytoskeleton changes. VK 3 treatment damages the cell nucleus and organelles, leads to the redistribution of the organelles in the perikaryon as a consequence of cytoskeletal damage, and results in cytoplasmic self-excisions. After VC:VK 3 treatment, the cells show exaggerated alterations characteristic of each vitamin treatment alone, including damaged mitochondria, self-excision of organelle-free pieces of cytoplasm, and extrusion of the perikaryon containing a nucleus surrounded by the damaged organelles. The nuclear envelope appears intact and contains chromatin that decondenses and dissipates. During the cellular demise that concludes with apparent karyolysis, the cells significantly decrease their size and alter their shape. However, the cisterns of rough endoplasmic reticulum are undamaged, but may become dilated. Since the cellular phenomena leading to cell death differ morphologically from apoptosis and necrosis, but entail selfcutting without nuclear bodies, this new form of cell death was called autoschizis. In addition, gel electrophoresis and Feulgen staining demonstrate that autoschizis is accompanied by random DNA degeneration.

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Increased DNA chain breakage by combined action of bleomycin and superoxide radical

Cited by 178 publications

References 21 publications

Mode of Action of Quindoxin and Substituted Quinoxaline-di- N -Oxides on Escherichia coli

Mode of Action of Quindoxin and Substituted Quinoxaline-di- N -Oxides on Escherichia coli

Modifiers of free radicals inhibit in vitro the oncogenic actions of x-rays, bleomycin, and the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.

Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment

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