NMR spectroscopy analysis of phosphorus metabolites and the effect of adriamycin on these metabolite levels in an adriamycin-sensitive and -resistant human small cell lung carcinoma cell line

Jong, de Steven; Mulder, Nanno; Vries, de Elisabeth G. E.; Robillard, G.T.

doi:10.1038/bjc.1991.50

Cited by 11 publications

(6 citation statements)

References 19 publications

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“…For example, in T47D clone 11 human breast cancer cells, adriamycin induced a fast transient increase of 30 -50% in the NTP levels before cell death (4,8). The adriamycin-induced increase in the NTP levels was also observed in small cell lung carcinoma cultures (5). Other chemotherapeutic drugs such as cisplatin in human ovarian carcinoma (6) and hypoxanthine with methotrexate in rat lymphoma cells and in L1210 mouse leukemia cells (7) also induced an increase in ATP levels.…”

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confidence: 69%

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Reversible Induction of ATP Synthesis by DNA Damage and Repair in Escherichia coli

Dahan-Grobgeld¹,

Livneh²,

Maretzek³

et al. 1998

Journal of Biological Chemistry

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Early metabolic events in Escherichia coli exposed to nalidixic acid, a topoisomerase II inhibitor and an inducer of the SOS system, were investigated by in vivo NMR spectroscopy, a technique that permits monitoring of bacteria under controlled physiological conditions. The energetics of AB1157 (wild type) and of its isogenic, SOS-defective mutants, recBC, lexA, and ⌬recA, were studied by 31 P and 19 F NMR before, during, and after exposure to nalidixic acid. The content of the NTP in E. coli embedded in agarose beads and perfused at 36°C was found to be 4.3 ؎ 1.1 ؋ 10 ؊18 mol/cell, yielding a concentration of ϳ2.7 ؎ 0.7 mM. Nalidixic acid induced in the wild type and mutants a rapid 2-fold increase in the content of the NTP, predominantly ATP. This induction did not involve synthesis of uracil derivatives or breakdown of RNA and caused cell proliferation to stop. Removal of nalidixic acid after 40 min of treatment rescued the cells and resulted in a decrease of ATP to control levels and resumption of proliferation. However, in ⌬recA cells, which were more sensitive to the activity of the drug, ATP elevation could not be reversed, and ATP content continued to increase faster than in control cells. The results ruled out association between the elevation of ATP and the induction of the SOS system and suggested involvement of a process reminiscent of apoptosis in the stimulation of ATP synthesis. Thus, the presence of the RecA protein was found to be essential for reversing the ATP increase and cell rescue, possibly by its function in repair of DNA damage.Several antitumor and antibacterial drugs were shown to induce a rapid elevation in the total pool of the NTPs in prokaryotes and eukaryotes (1-7). In Escherichia coli, bleomycin and UV radiation, which are also bacterial SOS activators, were shown to induce a rapid, transient, and 2-fold increase in ATP concentration (1, 2). The pronounced elevation of ATP was shown to be independent of oxidative phosphorylation and was therefore attributed to an unknown intracellular phosphorylation pathway (1). In addition, with UV a delayed and substantially smaller increase in ATP was found to occur in the recBC mutant (1), whereas a complete inhibition of this increase occurred in a recBC mutant treated with bleomycin (2). In wild type, Within ϳ30 min of induction of ATP, the bacteria entered a recovery phase, and ATP rapidly declined to baseline levels (1-3). However, in the mutants with impaired SOS activity, such as recA13 (defective RecA protein), recA430 (deficient RecA protease activity), and lexA1 (cleavage resistant LexA repressor), recovery was impeded, and ATP levels remained elevated (1-3). These results indicated involvement of the SOS pathway in the return to normal NTP levels, i.e. the recovery phase (3).The rapid increase in ATP after damage to DNA is not unique to prokaryotic cells and also occurs in mammalian cancer cells in response to chemotherapy (4 -7). For example, in T47D clone 11 human breast cancer cells, adriamycin induced a fast transient increase ...

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confidence: 69%

“…Several antitumor and antibacterial drugs were shown to induce a rapid elevation in the total pool of the NTPs in prokaryotes and eukaryotes (1)(2)(3)(4)(5)(6)(7). In Escherichia coli, bleomycin and UV radiation, which are also bacterial SOS activators, were shown to induce a rapid, transient, and 2-fold increase in ATP concentration (1,2).…”

mentioning

confidence: 99%

Reversible Induction of ATP Synthesis by DNA Damage and Repair in Escherichia coli

Dahan-Grobgeld¹,

Livneh²,

Maretzek³

et al. 1998

Journal of Biological Chemistry

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“…As we will see in Section 2.3.2. on metabolites, 31 P NMR is convenient in cells because of its relatively good sensitivity when present in small molecules and the small number of observable signals. Hence, 31 P NMR and the survey of ATP chemical shifts has been used since the late 1970's [311,312] to measure the intracellular free Mg 2+ and the ATP:Mg 2+ population in erythrocytes [202,[312][313][314][315][316][317], lymphocytes [318], Ehrlich ascites tumor cells [319], cultured mammalian cells [320,321], animal tissues [322][323][324][325][326][327], in worms, amoebae or sea snail [328][329][330], and more recently in MRI/MRS studies [331][332][333][334][335]. These 31 P NMR studies have regularly reported that the concentration of free intracellular Mg 2+ is only $0.3-0.6 mM in mammalian cells, while the total concentration of 10-20 mM in most cells [336] (with an exception: only $2 mM in erythrocytes that contain low quantities of nucleic acids).…”

Section: Mg 2+mentioning

confidence: 99%

In-cell NMR: Why and how?

Theillet

Luchinat

2022

Progress in Nuclear Magnetic Resonance Spectroscopy

105

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“…For example, Jiang et al (1993) found significantly lower taurine content in a drug-resistant T-lymphoid leukaemia cell line compared with its drug-sensitive parental counterpart. De Jong et al (1991) used 31p_ and IH-NMR spectroscopy to measure phospholipid metabolism in a doxorubicin-resistant human small-cell lung carcinoma cell line and the corresponding doxorubicin-sensitive parental cell line. This is the first report, to our knowledge, in which NMR has been used to study glutathione homeostasis in relation to drug resistance.…”

Section: Resultsmentioning

confidence: 99%

Menadione-resistant Chinese hamster ovary cells have an increased capacity for glutathione synthesis

Vallis

Reglinski²,

Garner³

et al. 1997

Br J Cancer

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Summary A cell line (MRc4O) resistant to the model quinone compound, menadione, has been isolated from a parental Chinese hamster ovary cell line (CHO-K1). The known relationship between menadione toxicity and glutathione (GSH) depletion led us to investigate whether the mechanism of resistance of MRc40 was related to alteration in GSH homeostasis. Intracellular concentrations of GSH and cysteine (CySH) were twofold and 3.2-fold greater in MRc40 than in CHO-Kl. Following exposure to menadione, GSH and CySH were depleted, but subsequent recovery of thiols was more rapid and of greater magnitude in MRc40 than in CHO-Kl. Twelve hours after exposure to menadione, the concentrations of GSH and CySH were 9.7-and 4.2-fold greater in MRc40 than in CHO-Kl. Using nuclear magnetic resonance (NMR) spectroscopy, we observed the in situ removal of menadione from cell suspensions of CHO-Kl and MRc40. However, only in CHO-Kl did we observe concomitant depletion of NMR-visible GSH. We conclude that the perturbation of GSH metabolism contributes to the resistant phenotype and is an important characteristic of menadione-resistant CHO cells.

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NMR spectroscopy analysis of phosphorus metabolites and the effect of adriamycin on these metabolite levels in an adriamycin-sensitive and -resistant human small cell lung carcinoma cell line

Cited by 11 publications

References 19 publications

Reversible Induction of ATP Synthesis by DNA Damage and Repair in Escherichia coli

Reversible Induction of ATP Synthesis by DNA Damage and Repair in Escherichia coli

In-cell NMR: Why and how?

Menadione-resistant Chinese hamster ovary cells have an increased capacity for glutathione synthesis

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