Effect of nitrogen mustard, a vesicant agent, on lymphocyte energy metabolism
-
Levent Kenar
Abstract
Background: The vesicant agents sulfur and nitrogen mustards, which contain chloroethyl groups, are potent inhibitors of DNA synthesis and cell growth, likely changing the utilization of anaerobic glycolysis for energy generation.
Methods: To investigate the effect of nitrogen mustard on cellular energy metabolism, lymphocytes treated with increasing doses of mechlorethamine (HN2), a nitrogen mustard and an analogue of sulfur mustard, were incubated with radiolabeled glucose. The rates of aerobic and anaerobic glycolysis were then determined.
Results: Glycogen consumption was significantly higher in cells treated with HN2 in a dose-dependent manner compared to untreated cells. Similarly, the amount of end-product lactate was increased, but CO2 was reduced in HN2-treated cells.
Conclusions: Lymphocytes normally use aerobic glycolysis under aerobic conditions, but energy metabolism predominantly involved anaerobic glycolysis after severe intoxication with mustard agent.
Clin Chem Lab Med 2006;44:1253–7.
References
1. Kenar L, Karayilanoglu T, Yuksel A, Gunhan O, Kose S, Kurt B. Evaluation of protective ointments used against dermal effects of nitrogen mustard, a vesicant warfare agent. Mil Med 2005; 170:1–6.10.7205/MILMED.170.1.1Search in Google Scholar
2. Platteborze PL. Effects of sulfur mustard on transcription in human epidermal keratinocytes: analysis by mRNA differential display. J Appl Toxicol 2003; 23:249–54.10.1002/jat.914Search in Google Scholar
3. Mol MA, de Vries R, Kluivers AW. Effects of nicotinamide on biochemical changes and microblistering induced by sulfur mustard in human skin organ cultures. Toxicol Appl Pharmacol 1991; 107:439–49.10.1016/0041-008X(91)90307-ZSearch in Google Scholar
4. Meier HL, Millard C, Moser J. Poly(ADP-ribose) polymerase inhibitors regulate the mechanism of sulfur mustard-initiated cell death in human lymphocytes. J Appl Toxicol 2000; 20:S93–100.10.1002/1099-1263(200012)20:1+<::AID-JAT664>3.3.CO;2-DSearch in Google Scholar
5. Weltin D, Aupeix K, Iltis C, Cuillerot JM, Dufour P, Marchal J, et al. N-Acetylcysteine protects lymphocytes from nitrogen mustard-induced apoptosis. Biochem Pharmacol 1996; 51:1123–9.10.1016/0006-2952(96)83389-2Search in Google Scholar
6. Elsayed NM, Omaye ST, Klain GJ, Korte DW Jr. Free radical-mediated lung response to the monofunctional, sulfur mustard butyl 2-chloroethyl sulfide after subcutaneous injection. Toxicology 1992; 72:153–65.10.1016/0300-483X(92)90109-RSearch in Google Scholar
7. Omaye ST, Elsayed NM, Klain GJ, Korte DW Jr. Metabolic changes in mouse kidney after subcutaneous injection of butyl 2-chloroethyl sulfide. J Toxicol Environ Health 1991; 33:19–27.10.1080/15287399109531502Search in Google Scholar
8. Champe PC, Harvey RA, Ferrier DR. Glycolysis. In: Champe P, Harvey R, Ferrier D, editors. Lippincott's illustrated reviews: biochemistry, 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2004:89–106.Search in Google Scholar
9. Sacks DB. Carbohydrates. In: Burtis CA, Ashwood ER, editors. Tietz textbook of clinical chemistry, 3rd ed. Philadelphia, PA: Saunders, 1999:754–66.Search in Google Scholar
10. Dienel GA, Hertz L. Glucose and lactate metabolism during brain activation. J Neurosci Res 2001; 66:824–38.10.1002/jnr.10079Search in Google Scholar
11. Rossignol R, Gilkerson R, Aggeler R, Yamagata K, Remington SJ, Capaldi RA. Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells. Cancer Res 2004; 64:985–93.10.1158/0008-5472.CAN-03-1101Search in Google Scholar
12. Raghunand N, Gatenby RA, Gillies RJ. Microenvironmental and cellular consequences of altered blood flow in tumours. Br J Radiol 2003; 76:11–22.10.1259/bjr/12913493Search in Google Scholar
13. Tielens AG, Pas FA, Heuvel JM, van den Bergh SG. The aerobic energy metabolism of Schistosoma mansoni miracidia. Mol Biochem Parasitol 1991; 46:181–4.10.1016/0166-6851(91)90211-NSearch in Google Scholar
14. Tielens AG. Energy generation in parasitic helminths. Parasitol Today 1994; 10:346–52.10.1016/0169-4758(94)90245-3Search in Google Scholar
15. Boyunaga H, Schmitz MG, Brouwers JF, Van Hellemond JJ, Tielens AG. Fasciola hepatica miracidia are dependent on respiration and endogenous glycogen degradation for their energy generation. Parasitology 2001; 122:169–73.10.1017/S0031182001007211Search in Google Scholar
16. Hardie DG. Metabolic control: a new solution to an old problem. Curr Biol 2000; 19:757–9.10.1016/S0960-9822(00)00744-2Search in Google Scholar
17. Kharitonov SA, Barnes PJ. Biomarkers of some pulmonary diseases in exhaled breath. Biomarkers 2002; 7:1–32.10.1080/13547500110104233Search in Google Scholar
18. Marino MT. Use of surrogate markers for drugs of military importance. Mil Med 1998; 163:742–6.10.1093/milmed/163.11.743Search in Google Scholar
19. Koller A, Kaplan LA. Total serum protein. In: Pesce AJ, Kaplan LA, editors. Methods in clinical chemistry. St. Louis, MO: Mosby, 1987:1134–44.Search in Google Scholar
20. Hassid WZ, Abraham S. Chemical procedures for analysis of polysaccharides. In: Colowick SP, Kaplan NO, editors. Methods in enzymology, vol. 3. New York: Academic Press, 1957:34–7.Search in Google Scholar
21. Kenar L, Karayilanoglu T, Kose S. Laboratory conditions and safety in a chemical warfare agent analysis and research laboratory. Mil Med 2002; 167:628–33.10.1093/milmed/167.8.628Search in Google Scholar
22. Meier HL, Gross CL, Papirmeister B. 2,2′-Dichlorodiethyl sulfide (sulfur mustard) decreases NAD+ levels in human leukocytes. Toxicol Lett 1987; 39:109–22.10.1016/0378-4274(87)90263-3Search in Google Scholar
23. Meier HL, Johnson JB. Inhibitors of poly(ADP-ribose)polymerase prevent the cytotoxic effects induced in human lymphocytes by the alkylating agent, 2,2′-dichlorodiethyl sulfide (sulfur mustard, HD). Toxicol Appl Pharmacol 1992; 13:234–9.Search in Google Scholar
24. Chesney J, Mitchell R, Benigni F, Bacher M, Spiegel L, Al-Abed Y, et al. An inducible gene product for 6-phosphofructo-2-kinase with an AU-rich instability element: role in tumor cell glycolysis and the Warburg effect. Proc Natl Acad Sci USA 1999; 96:3047–52.10.1073/pnas.96.6.3047Search in Google Scholar PubMed PubMed Central
25. Dang CV, Lewis BC, Dolde C, Dang G, Shim H. Oncogenes in tumor metabolism, tumorigenesis, and apoptosis. J Bioenerg Biomembr 1997; 29:345–54.10.1023/A:1022446730452Search in Google Scholar
26. Seto S, Carrerra CJ, Kubota M, Watson B, Carson DA. Mechanism of deoxyadenosine and 2-chlorodeoxyadenosine toxicity to nondividing human lymphocytes. J Clin Invest 1985; 75:135–42.10.1172/JCI111710Search in Google Scholar
27. Oton R, Mendonca JR, Curi R. Diabetes causes marked changes in lymphocyte metabolism. J Endocrinol 2002; 174:55–61.10.1677/joe.0.1740055Search in Google Scholar
28. Moreno-Aurioles VR, Montano R, Conde M, Bustos R, Sobrino F. Streptozotocin-induced diabetes increases fructose 2,6-biphosphate levels and glucose metabolism in thymus lymphocytes. Life Sci 1996; 58:477–84.10.1016/0024-3205(95)02312-7Search in Google Scholar
29. Hochachka PW. Mechanism and evolution of hypoxia tolerance in humans. J Exp Biol 1998; 201:1243–54.10.1242/jeb.201.8.1243Search in Google Scholar PubMed
30. Scatena R, Bottoni P, Martorana GE, Ferrari F, De Sole P, Rossi C, et al. Mitochondrial respiratory chain dysfunction, a non-receptor-mediated effect of synthetic PPAR-ligands: biochemical and pharmacological implications. Biochem Biophys Res Commun 2004; 319:967–73.10.1016/j.bbrc.2004.05.072Search in Google Scholar PubMed
31. Mayes PA, Bender DA. The pentose phosphate pathway and other pathways of hexose metabolism. In: Murray RK, Granner DK, Mayes PA, Rodwell VW, editors. Harper's illustrated biochemistry, 26th ed. New York: McGraw-Hill, 2003:163–73.Search in Google Scholar
©2006 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Multiplexed testing in the autoimmunity laboratory
- Uncertainty calculation for calibrators and controls of laboratory diagnostic assays
- Westgard multirule for calculated laboratory tests
- Frequency of a single nucleotide (A2317G) and 56-bp variable number of tandem repeat polymorphisms within the deoxyribonuclease I gene in five ethnic populations
- The influence of genetic polymorphisms of cytochrome P450 3A5 and ABCB1 on starting dose- and weight-standardized tacrolimus trough concentrations after kidney transplantation in relation to renal function
- Apolipoprotein B gene 3′VNTR polymorphism: association with plasma lipids and coronary heart disease in Han Chinese
- Paraoxonase-1 (PON1) activity, but not PON1Q192R phenotype, is a predictor of coronary artery disease in a middle-aged Serbian population
- A modified method of prothrombin time/International Normalised Ratio determination in capillary blood and monitoring oral anticoagulant therapy
- Inhibition of the ubiquitin-proteasome system: a new avenue for atherosclerosis
- Lipid peroxidation and antioxidative status in β-thalassemia major patients with or without hepatitis C virus infection
- Role of serum S100B as a predictive marker of fatal outcome following isolated severe head injury or multitrauma in males
- Preanalytical and analytical variation of surface-enhanced laser desorption-ionization time-of-flight mass spectrometry of human serum
- Effect of nitrogen mustard, a vesicant agent, on lymphocyte energy metabolism
- Partitioning reference values of several Gaussian subpopulations with unequal prevalence – a procedure with computer program support
- Biovariability of plasma adiponectin
- Multicentre evaluation of a new point-of-care test for the determination of NT-proBNP in whole blood
- Innotrac Aio!: a point-of-care or a routine analyzer? Analytical performance and plasma/whole blood comparison
- Serologic associations of anti-cytoplasmic antibodies identified during anti-nuclear antibody testing
- The importance of metrological traceability on the validity of creatinine measurement as an index of renal function: International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)
- Effect of seropositive rheumatoid factor on cardiac troponin I measurement using the Access® Immunoassay Analyzer
Articles in the same Issue
- Multiplexed testing in the autoimmunity laboratory
- Uncertainty calculation for calibrators and controls of laboratory diagnostic assays
- Westgard multirule for calculated laboratory tests
- Frequency of a single nucleotide (A2317G) and 56-bp variable number of tandem repeat polymorphisms within the deoxyribonuclease I gene in five ethnic populations
- The influence of genetic polymorphisms of cytochrome P450 3A5 and ABCB1 on starting dose- and weight-standardized tacrolimus trough concentrations after kidney transplantation in relation to renal function
- Apolipoprotein B gene 3′VNTR polymorphism: association with plasma lipids and coronary heart disease in Han Chinese
- Paraoxonase-1 (PON1) activity, but not PON1Q192R phenotype, is a predictor of coronary artery disease in a middle-aged Serbian population
- A modified method of prothrombin time/International Normalised Ratio determination in capillary blood and monitoring oral anticoagulant therapy
- Inhibition of the ubiquitin-proteasome system: a new avenue for atherosclerosis
- Lipid peroxidation and antioxidative status in β-thalassemia major patients with or without hepatitis C virus infection
- Role of serum S100B as a predictive marker of fatal outcome following isolated severe head injury or multitrauma in males
- Preanalytical and analytical variation of surface-enhanced laser desorption-ionization time-of-flight mass spectrometry of human serum
- Effect of nitrogen mustard, a vesicant agent, on lymphocyte energy metabolism
- Partitioning reference values of several Gaussian subpopulations with unequal prevalence – a procedure with computer program support
- Biovariability of plasma adiponectin
- Multicentre evaluation of a new point-of-care test for the determination of NT-proBNP in whole blood
- Innotrac Aio!: a point-of-care or a routine analyzer? Analytical performance and plasma/whole blood comparison
- Serologic associations of anti-cytoplasmic antibodies identified during anti-nuclear antibody testing
- The importance of metrological traceability on the validity of creatinine measurement as an index of renal function: International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)
- Effect of seropositive rheumatoid factor on cardiac troponin I measurement using the Access® Immunoassay Analyzer
