chiniofon and Leukemia--Lymphoid

Hemin (ferriprotoporphyrin IX), the oxidized prosthetic group of hemoglobin, is a source of potentially cytotoxic iron, but in chronic low doses can induce cytoprotection against iron-stimulated oxidative stress. The latter property of hemin has been examined, using murine L1210 cells and three different oxidant generating systems: (i) glucose/glucose oxidase, (ii) near-ultraviolet irradiation, and (iii) dye-mediated photodynamic action. Cells treated with the lipophilic iron donor ferric-8-hydroxyquinoline, Fe(HQ)2 (1 microM, 30 min) were found to be more sensitive to oxidative killing than nontreated controls. However, cells challenged after long-term (20-24 h) exposure to hemin (10 microM) were substantially more resistant than controls and were sensitized far less by Fe(HQ)2. Immunoblot analyses of 24-h hemin-treated cells indicated that the ferritin heavy (H) subunit was elevated 12- to 15-fold, whereas the light (L) subunit was essentially unchanged. Experiments carried out with 55Fe(HQ)2 showed that iron uptake capacity of cells was greatly enhanced after hemin treatment. More specifically, hemin-stimulated cells were found to contain approximately 9 times more immunoprecipitable ferritin iron after incubation with saturating levels (4-5 microM) of 55Fe(HQ)2 and approximately 3 times more iron per ferritin molecule compared with nonstimulated controls. The nonferritin iron content of the latter was estimated to be approximately 40 times greater than that of the former following low-level (0.5 microM) 55Fe(HQ)2 treatment. These results are consistent with the idea that induced ferritin, enriched in H-chain, sequesters redox active iron rapidly and copiously, thereby enhancing cellular resistance to oxidants.

Topics: Animals; Antineoplastic Agents; Biological Transport; Dose-Response Relationship, Radiation; Drug Resistance; Ferric Compounds; Ferritins; Gene Expression Regulation, Neoplastic; Hemin; Hydroxyquinolines; Iron; Leukemia, Lymphoid; Mice; Oxidative Stress; Tumor Cells, Cultured; Ultraviolet Rays; Up-Regulation

The in vitro use of the radioisotope indium 111 (111In) was examined as a radiolabel for lymphocytes obtained from both normal individuals and patients with a variety of lymphoid malignancies. Successful cell labeling requires a chelator. The traditional agent oxine, has proved to be toxic to the lymphoid lineage. Cellular uptake of 111In mediated by the chelator oxine was compared with that of a new chelator, tropolone. Oxine provided better labeling efficiency (48%) than tropolone (35%) for the labeling of normal lymphocytes. By contrast, lymphocytes from patients with chronic lymphocytic leukemia had a nearly twofold greater labeling efficiency when tropolone was substituted for oxine. Further studies demonstrated that tropolone induced functional injury to lymphocytes when mitogenic response to concanavalin A, pokeweed mitogen, and phytohemagglutinin was assessed. Similar toxicity was found when tropolone was compared with oxine. In addition, tropolone produced damaging structural changes seen by both scanning and transmission electron microscopic examination. These changes were both variable and not predictable. Shortening of the incubation time of the chelator with the cell provided the least amount of cellular injury. These findings suggest that tropolone be used as an alternative mediator of lymphocyte labeling with 111In only under critically defined conditions.

Topics: Cells, Cultured; Cycloheptanes; Hodgkin Disease; Humans; Hydroxyquinolines; Indium; Leukemia; Leukemia, Lymphoid; Lymphocyte Activation; Lymphocytes; Lymphoma; Microscopy, Electron; Microscopy, Electron, Scanning; Organometallic Compounds; Oxyquinoline; Tropolone

Topics: Aged; Female; Humans; Hydroxyquinolines; Indium; Kinetics; Leukemia, Lymphoid; Lymphocytes; Male; Middle Aged; Organometallic Compounds; Oxyquinoline

One hundred twenty-nine 111In-oxine-labeled leukocyte scintiscans have been performed in 117 patients with cancer in order to diagnose localized infectious disease. Of the 115 contributive scans, 40 were in patients with localizing signs, whereas in 75 fever of unknown origin constituted the indication for this examination. The overall specificity of the method was 95.4%, the overall sensitivity 86%, and the global accuracy 91.3%. In 10 cases with localizing signs, the 111In-oxine granulocyte scintigram allowed exclusion of the diagnosis of infection, whereas in 17 instances without localizing signs, a focal infectious process was demonstrated. Heterologous donor leukocytes were used successfully in five instances. With the exception of accumulation of label at the site of an osteolytic metastasis in one case, no uptake was observed in primary or secondary tumors. It is concluded that 111In-oxine-labeled leukocytes constitute a valuable tool in the diagnosis and localization of infection in patients with malignant disease.

Topics: Bacterial Infections; Bone Neoplasms; Diagnosis, Differential; False Negative Reactions; Female; Humans; Hydroxyquinolines; Indium; Leukemia, Lymphoid; Leukocytes; Liver Neoplasms; Lymphoma; Neoplasms; Organometallic Compounds; Oxyquinoline; Radioisotopes; Radionuclide Imaging; Rectal Neoplasms; Uterine Cervical Neoplasms

Topics: Adolescent; Adult; Aged; B-Lymphocytes; Humans; Hydroxyquinolines; Indium; Kinetics; Leukemia, Lymphoid; Lymphocytes; Lymphoma; Male; Middle Aged; Organometallic Compounds; Oxyquinoline; Radionuclide Imaging; T-Lymphocytes; Tissue Distribution

Topics: Blood Platelets; Cell Survival; Female; Humans; Hydroxyquinolines; Indium; Leukemia, Lymphoid; Male; Oxyquinoline; Radioisotopes; Thrombocytopenia