Antitumor activities of iodoacetate and dimethylsulphoxide against solid Ehrlich carcinoma growth in mice.

Treatment of tumor-bearing mice with LD12.5 values of iodoacetate; IAA (1.84 mg/100 g b.w.) and/or dimethylsulphoxide; DMSO (350 mg/100 g b.w.) significantly increased the cumulative mean survival time and percentage of survivors and reduced the mean tumor weight, compared to tumor-bearing controls, however, a more pronounced effect is recorded in the combined treatment. Also, an increase in the life span (ILS%) and tumor growth inhibition ratio (T/C%) are reported and amounted to 145.78 and 43.80%, 195.54 and 61.30% and 220.77 and 78.40% in IAA, DMSO and combined-treated groups, respectively. Results obtained from biochemical studies reveal that a single IAA treatment of tumor-bearing mice significantly increased the levels of plasma lactate dehydrogenase (LDH) activity, while it also significantly decreased the levels of plasma glucose and liver total protein, RNA and DNA, compared to normal controls. On the other hand, a single DMSO treatment significantly elevated the activities of blood antioxidant enzymes, i.e. glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PDH) and decreased the liver RNA and DNA levels. Combined treatment increased significantly the levels of plasma LDH and erythrocytes G6PDH activities, as well as liver glycogen, and in contrast it decreased the levels of liver total protein, RNA and DNA, compared to normal controls.

[1]  S. Muhtaroğlu,et al.  The effects of dimethylsulfoxide on experimental hepatic ischemia. , 2000, Swiss surgery = Schweizer Chirurgie = Chirurgie suisse = Chirurgia svizzera.

[2]  C. C. Allain,et al.  Rapid single-step kinetic colorimetric assay for lactate dehydrogenase in serum. , 1973, Clinical chemistry.

[3]  Murray R. Spiegel,et al.  Schaum's Outline of Theory and Problems of Probability and Statistics , 1980 .

[4]  S. Orrenius,et al.  Role of thiols in protection against biological reactive intermediates. , 1986, Advances in experimental medicine and biology.

[5]  J. Carretero,et al.  Changes in glutathione status and the antioxidant system in blood and in cancer cells associate with tumour growth in vivo. , 1999, Free radical biology & medicine.

[6]  J. H. Quastel,et al.  Effects of Metabolic Inhibitors on Energy Metabolism of Ehrlich Ascites Carcinoma Cells , 1965, Nature.

[7]  W S MacGregor,et al.  THE CHEMICAL AND PHYSICAL PROPERTIES OF DMSO , 1967, Annals of the New York Academy of Sciences.

[8]  F. Smith,et al.  COLORIMETRIC METHOD FOR DETER-MINATION OF SUGAR AND RELATED SUBSTANCE , 1956 .

[9]  G. Glenner,et al.  HISTOCHEMICAL DEMONSTRATION OF URIDINE DIPHOSPHATE GLUCOSE-GLYCOGEN TRANSFERASE IN ANIMAL TISSUES , 1961, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[10]  G. Sponer,et al.  Acute toxicity of various solvents in the mouse and rat. LD50 of ethanol, diethylacetamide, dimethylformamide, dimethylsulfoxide, glycerine, N-methylpyrrolidone, polyethylene glycol 400, 1,2-propanediol and Tween 20. , 1976, Arzneimittel-Forschung.

[11]  R. Glazer,et al.  Iodoacetate inhibition of lactate production and lipid, protein, ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) synthesis in newborn rat brain cortex slices. , 1971, Biochemical pharmacology.

[12]  E. Racker,et al.  Regulatory Mechanisms in Carbohydrate Metabolism , 2003 .

[13]  F A Fahim,et al.  Serum LDH and ALP isozyme activities in mice bearing solid Ehrlich carcinoma and/or treated with the maximum tolerated dose (MTD) of aloin. , 1997, Disease markers.

[14]  W. Rose,et al.  Immunotherapy of Madison 109 lung carcinoma and other murine tumors using lentinan. , 1984, Cancer research.

[15]  L. Moldawer,et al.  Plasma protein synthesis in experimental cancer compared to paraneoplastic conditions, including monokine administration. , 1987, Cancer research.

[16]  J. Ruysschaert,et al.  Increasing therapeutic effect and reducing toxicity of doxorubicin by N-acyl dehydroalanines. , 1989, European journal of cancer & clinical oncology.

[17]  Ernest Beutler,et al.  Red Cell Metabolism: A Manual of Biochemical Methods , 1975 .

[18]  W. Haschek,et al.  Protection by dimethylsulfoxide against acetaminophen-induced hepatic, but not respiratory toxicity in the mouse. , 1988, Toxicology and applied pharmacology.

[19]  R. Geran,et al.  PROTOCOLS FOR SCREENING CHEMICAL AGENTS AND NATURAL PRODUCTS AGAINST ANIMAL TUMORS AND OTHER BIOLOGICAL SYSTEMS , 1972 .

[20]  佐藤 壽.  Estimation of nucleic acids in microorganisms , 1953 .

[21]  P. Higgins.  Characterization of the growth inhibited substate induced in murine hepatic tumor cells during in vitro exposure to dimethylsulfoxide , 1986, International journal of cancer.

[22]  L. Vaughan,et al.  Elevated pentose cycle and glucuronyltransferase in daunorubicin-resistant P388 cells. , 1990, Cancer research.

[23]  M. Suthanthiran,et al.  Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[24]  D. Blake,et al.  Reactive oxygen metabolites and the human myocardium. , 1989, British heart journal.

[25]  G. Brownell,et al.  Comparative measurement of regional blood flow, oxygen and glucose utilisation in soft tissue tumour of rabbit with positron imaging. , 1985, The British journal of radiology.

[26]  M. Cascante,et al.  Nonoxidative pentose phosphate pathways and their direct role in ribose synthesis in tumors: is cancer a disease of cellular glucose metabolism? , 1998, Medical hypotheses.

[27]  W. Valentine,et al.  Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. , 1967, The Journal of laboratory and clinical medicine.

[28]  G. Bengtsson,et al.  The effect of Ehrlich ascites tumour growth on lactate dehydrogenase activities in tissues and physiological fluids of tumour bearing mice. , 1981, The International journal of biochemistry.

[29]  P. Trinder.  Determination of Glucose in Blood Using Glucose Oxidase with an Alternative Oxygen Acceptor , 1969 .

[30]  L. Reed,et al.  A SIMPLE METHOD OF ESTIMATING FIFTY PER CENT ENDPOINTS , 1938 .

[31]  J. Williams,et al.  Glycolytic, glutaminolytic and pentose-phosphate pathways in promyelocytic HL60 and DMSO-differentiated HL60 cells. , 1993, Biochemistry and molecular biology international.

[32]  P. Higgins,et al.  Dimethylsulfoxide-induced alterations in the growth properties and protein composition of in vitro-propagated murine hepatoma cells. , 1982, Oncology.

[33]  E. Kosower,et al.  The glutathione status of cells. , 1978, International review of cytology.

[34]  N. Tolbert,et al.  A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. , 1978, Analytical biochemistry.

[35]  T. Scherstén,et al.  Protein synthesis in liver tissue under the influence of a methylcholanthrene-induced sarcoma in mice. , 1979, Cancer research.

[36]  T. Scherstén,et al.  A comparative study of the influence of malignant tumor on host metabolism in mice and man. Evaluation of an experimental model , 1978, Cancer.

[37]  J. A. Badwey,et al.  Active oxygen species and the functions of phagocytic leukocytes. , 1980, Annual review of biochemistry.