ascorbic-acid and Leukemia--Lymphoid

Topics: Ascorbic Acid; Dehydroascorbic Acid; Electron Spin Resonance Spectroscopy; Erythrocytes; Free Radicals; Glutathione; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Oxidation-Reduction; Potassium; Sodium

Modulating the amount of radiation-induced apoptosis by administering antioxidant vitamins offers a possible way to influence radiation-induced side effects in normal tissues. Therefore, we investigated the effect of beta-carotene, vitamin C and alpha-tocopherol on radiation-induced apoptosis in cells in culture. Human T-lymphoblastic MOLT-3 cells were irradiated with a dose of 3 Gy 1 h after or immediately prior to the addition of vitamins in three concentrations (0.01 microM, 1 microM and 100 microM). Eight hours later, apoptosis was scored morphologically by staining the nuclear DNA with Hoechst 33342. When given prior to irradiation, beta-carotene and vitamin E reduced the amount of radiation-induced apoptosis significantly at concentrations of 0.01 microM and 1 microM. In contrast, vitamin C did not show any protective effect when given at these two concentrations and caused a slight but significant radiosensitization at 100 microM. At 0.01 microM, all combinations of two vitamins showed a protective effect. This was also observed for the combination of all three vitamins at concentrations of 0.01 and 1 microM. When given immediately after irradiation, each of the three vitamins showed a protective effect at 0.01 microM. In addition, the combination of alpha-tocopherol and vitamin C reduced radiation-induced apoptosis slightly when given at 1 microM. In all other cases, no statistically significant modulation of radiation-induced apoptosis was observed. In our experimental system, the protective effect of beta-carotene and vitamin E was dependent on concentration and occurred only in the micromolar and sub-micromolar concentration range, while vitamin C alone, but not in combinations, had a sensitizing effect, thus arguing for a careful consideration of vitamin concentrations in clinical settings.

Topics: alpha-Tocopherol; Antioxidants; Apoptosis; Ascorbic Acid; beta Carotene; Cell Line, Tumor; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Humans; Leukemia, Lymphoid; Radiation Dosage; Radiation Tolerance; Vitamins

Topics: Acute Disease; Adult; Antigens, CD; Antineoplastic Agents; Antioxidants; Arsenic Trioxide; Arsenicals; Ascorbic Acid; Burkitt Lymphoma; Drug Therapy, Combination; Female; Humans; L-Lactate Dehydrogenase; Leukemia, Lymphoid; Oxides; Salvage Therapy; Treatment Outcome

Electron spin resonance (ESR) spectra of lyophilized erythrocytes obtained from patients with acute myeloid leukemia (AML) show, in comparison to controls, a characteristic change especially in the low-field region of the spectrum concomitant with a reduction of the spin concentration. This effect can be simulated by addition of SH-containing substances (e.g. reduced glutathione or cysteine) to healthy erythrocytes. S-S containing compounds exhibit no effect. Since SH-containing substances can hardly permeate plasma membranes, the membrane surface seems to be defective in the case of "AML" erythrocytes. Furthermore, it can be concluded that the concentration of SH-containing substances, such as cysteine, is increased in the plasma of AML-patients, which could be confirmed by HPLC-measurements. In the case of a successful treatment of the patients with alexan, daunoblastin, and thioguanine the spin concentration increased again and the resulting ESR spectrum is very similar to the control spectrum. It should be pointed out, that the ascorbic acid concentration is very low in both plasma and erythrocytes of AML patients.

Topics: Ascorbic Acid; Electron Spin Resonance Spectroscopy; Erythrocytes; Glutathione; Glycoproteins; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Sulfhydryl Compounds

Since mice can synthesize ascorbic acid but man cannot, the ascorbate status in murine and human leukaemia was compared. The decline in plasma ascorbate concentration in both cases indicates that vitamin C deficiency occurs in malignancy. Analysis of tissue ascorbate values in mice also indicated that an enhanced rate of utilization of this vitamin occurs during malignancy, as does an increased rate of excretion, and both events may be responsible for vitamin C deficiency. The hepatic ascorbate values suggest an endeavour by the animals to compensate for the loss through increased synthesis and storage of the vitamin, at least in the early stages of the disease.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Kidney; Leukemia, Experimental; Leukemia, Lymphoid; Leukemia, Myeloid; Liver; Mice; Spleen; Tissue Distribution

Dehydroascorbic acid is the principal form for the cellular uptake by blood cells of vitamin C. Since previous studies from this laboratory had shown a higher content of ascorbic acid and dehydroascorbic acid (DHA) in chronic lymphocytic leukemia (CLL) lymphocytes when compared to their normal counterparts, DHA uptake was characterized using these cells. The affinities of CLL and normal lymphocytes for DHA uptake were similar, as demonstrated by the Km values of 3.7 and 3.5 mM, respectively. Differences were found in other kinetic constants of DHA uptake. The Vmax for normal lymphocytes, 634 mumol/liter cell H2O/min, was approximately twice that of CLL cells, 392 mumol/liter cell H2O/min. In addition, the initial velocity and the maximal DHA uptake by normal lymphocytes were greater than that of CLL lymphocytes. These differences were not simply a reflection of lymphocyte subsets since CLL B-cells demonstrated lower uptake rates than did normal B-cells whereas CLL T-cells were similar to their normal counterparts. The alterations appear to be specific for the leukemic B-cell since they were not shared by neoplastic cells from two patients with T-cell CLL. When analyzed in light of the 3-fold greater cellular DHA and ascorbic acid content in B-cell CLL as compared to normal lymphocytes, these kinetic parameters support the occurrence of a concentration-dependent transport system for DHA. We conclude that the DHA uptake properties of CLL lymphocytes of B-cell origin serves to distinguish this lineage from T-cell CLL or normal lymphocytes.

Topics: Ascorbic Acid; Biological Transport; Cytosol; Dehydroascorbic Acid; Humans; Kinetics; Leukemia, Lymphoid; Lymphocytes

ESR investigations on lyophilized systems have shown that the signal at g = 2.005 can be explained by an interaction between Na+ or K+ and the anionic ascorbyl radical. The unpaired electron is probably localized near the C(4) region and is produced by a cleavage of an H atom belonging to a water molecule bound tightly to C(4). Experiments on aqueous samples revealed that ascorbic acid in its radical configuration and in its highest concentration exists only at physiological pH and temperature. An additional splitting is obtained by the ring formation between C(3) and C(6)-OH. The coupling constants of the triplets produced by the CH2-6 protons differ between ascorbic acid and isoascorbic acid. Thus, the ESR technique can be applied for an easy distinction between these two epimers.

Topics: Ascorbic Acid; Chemical Phenomena; Chemistry; Dehydroascorbic Acid; Electron Spin Resonance Spectroscopy; Erythrocytes; Free Radicals; Humans; Leukemia, Lymphoid

A method for the assay of dehydroascorbic acid using high-performance liquid chromatography with uv detection is described. The dehydroascorbic acid is separated from ascorbic acid and reduced with dithiothreitol, and is then quantitated as ascorbic acid following rechromatography. Since as little as 22 pmol can be detected, sensitivity is at least 40-fold greater than that of other currently available procedures. This method was used to measure the level of dehydroascorbic acid in normal and chronic lymphocytic leukemia lymphocytes. A significantly higher concentration of dehydroascorbic acid was found in leukemic (21.80 +/- 3.55 nmol/10(8) cells, mean +/- SE) than in normal lymphocytes (9.32 +/- 1.15 nmol/10(8) cells) (P less than 0.03). Analysis of extracts from normal B cell lymphocytes revealed comparable dehydroascorbic acid levels to unfractionated lymphocytes, indicating that the elevated level in chronic lymphocytic leukemia was not simply a reflection of the increased percentage of B lymphocytes in this disorder. These studies illustrate that the technique can be used to measure the dehydroascorbic acid content from sources where only scanty material is available or low levels are found.

Topics: Ascorbic Acid; B-Lymphocytes; Chromatography, High Pressure Liquid; Dehydroascorbic Acid; Humans; Leukemia, Lymphoid

Topics: Adolescent; Ascorbic Acid; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Leukemia, Lymphoid; Male; Tyrosine

Human lymphocyte extracts analyzed by high-performance liquid chromatography reveal a major UV-absorbing peak that was shown to be ascorbic acid by spectral, chemical, and enzymatic criteria. Because this peak appeared very prominent in the elution profile of chronic lymphocytic leukemia (CLL) lymphocyte extracts, we measured the ascorbic acid content in lymphocytes from the blood of normal subjects and untreated patients with chronic lymphocytic leukemia. A significantly higher concentration of 111 +/- 15.3 nmol per 10(8) cells (mean +/- SEM) was found in CLL lymphocytes than in normal blood lymphocytes, which contained 42.2 +/- 3.3 nmol per 10(8) cells. Selective enrichment with B and T cells showed that this difference was limited to the chronic lymphocytic leukemia B cell, which had a 5- to 15-fold higher content of ascorbic acid than normal B cells had. In contrast, the ascorbic acid level was similar in normal and CLL T cells. The very high ascorbic acid content provides the chronic lymphocytic leukemia B cell with a reducing substance that could react with oxidants or free radicals.

Topics: Ascorbic Acid; B-Lymphocytes; Chromatography, High Pressure Liquid; Humans; Leukemia, Lymphoid; Reference Values; Spectrophotometry, Ultraviolet; T-Lymphocytes

Topics: Adult; Aged; Antibodies; Ascorbic Acid; Bilirubin; Ceruloplasmin; Cholesterol; Fatty Acids, Nonesterified; Female; Glutathione; Humans; Leukemia, Lymphoid; Liver; Male; Middle Aged

Topics: Adult; Aged; Ascorbic Acid; Dehydroascorbic Acid; Humans; Leukemia, Lymphoid; Leukocytes; Middle Aged; Oxidation-Reduction

Topics: Adolescent; Ascorbic Acid; Child; Child, Preschool; Female; Humans; Leukemia, Lymphoid; Leukocytes; Male

Topics: Adolescent; Aged; Ascorbic Acid; Carcinoma; Child; Child, Preschool; Humans; Leukemia, Lymphoid; Leukocytes; Lung Neoplasms; Male; Middle Aged; Neoplasms; Skin; Skin Neoplasms

The platelet ascorbic acid concentration was measured in 26 normal subjects and found to be 20 times as high as in plasma. This is in agreement with previous reports in the literature. The platelets of patients with uraemia, leukaemia, and megaloblastic anaemia had a lower than normal platelet ascorbic acid content. In uraemia and megaloblastic anaemia the plasma ascorbic acid concentration was normal suggesting that a platelet defect may be responsible for the low platelet ascorbic acid content. In leukaemia the low platelet ascorbic acid content is probably secondary to a low plasma level.

Topics: Acute Disease; Adolescent; Adult; Anemia, Macrocytic; Ascorbic Acid; Blood Platelet Disorders; Blood Platelets; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Plasma; Uremia

Topics: Ascorbic Acid; Asparaginase; Bone Marrow; Bone Marrow Cells; Bone Marrow Examination; Child; Erythropoiesis; Hematopoiesis; Humans; Leukemia, Lymphoid; Penicillins; Vitamin K

Topics: Agglutination Tests; Ascorbic Acid; Candida; Candidiasis; Humans; Immunodiffusion; In Vitro Techniques; Iron; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma; Multiple Myeloma; Polycythemia Vera; Precipitin Tests; Transferrin

Topics: Ascorbic Acid; Chronic Disease; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Niacinamide; Pyridoxine; Riboflavin; Thiamine; Tryptophan; Vitamin B 12; Vitamin B 6 Deficiency; Vitamins

Topics: Animals; Ascorbic Acid; Leukemia; Leukemia, Experimental; Leukemia, Lymphoid; Lymphatic Vessels; Organic Chemicals; Vitamins