cyclic-gmp and Lymphoma--Non-Hodgkin

Thioproline (thiazolidino-4-carboxylic acid) is one of promising antineoplastic preparations arousing interest since several years. In view of controversies with respect to the mechanism of thioproline action it was tried to study the effects of the preparation on certain functions of lymphocytes. The experimental model included cultures of T and B lymphocytes obtained from 20 healthy blood donors. The cultures were exposed to various concentrations of thioproline for determining the incorporation of 3H-thymidine into the DNA of these cells, their viability and intracellular concentrations of cAMP and cGMP. The lymphocytes from these healthy donors served also as a control for B-cells isolated from 24 patients with lymphoproliferative syndromes. It was found that at low concentrations thioproline added to the culture of T-cells from healthy donors caused a slight increase of 3H-thymidine incorporation, but at high concentrations a strong cytotoxic effect on T-cells was noted. B-cells isolated from the peripheral blood of healthy subjects and from the patients were highly sensitive to thioproline. These observations demonstrated a cytotoxic effect of thioproline on T and B lymphocytes.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; B-Lymphocytes; Blood Donors; Cyclic AMP; Cyclic GMP; Cytotoxicity, Immunologic; DNA; Dose-Response Relationship, Drug; Female; Humans; In Vitro Techniques; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Male; Middle Aged; Models, Biological; T-Lymphocytes; Thiazoles; Thiazolidines

Topics: Adolescent; Adult; Antineoplastic Agents; Cyclic AMP; Cyclic GMP; Humans; In Vitro Techniques; Lymphocytes; Lymphoma, Non-Hodgkin; Reference Values; Thiazoles; Thiazolidines; Thymidine

Cyclic nucleotide levels, protein phosphotransferase activities, and cyclic nucleotide-binding proteins have been determined and partially characterized in the mouse lymphosarcoma P1798. This system is used as a model to understand the function of these activities in a rapidly proliferating cell. Adenosine 3':5'-monophosphate (cAMP) concentrations are 5-fold higher in the lymphosarcoma cells than in thymocytes. In both the thymocytes and malignant tissue, cAMP concentrations are increased by physiological concentrations of epinephrine and prostaglandin. The guanosine 3':5'-monophosphate (cGMP) level in the lymphosarcoma is 0.1 pmole/10(6) cells and is not modified by acetylcholine, prostaglandin F2alpha, or concanavalin A. Four protein phosphotransferase activities have been identified in the lymphosarcoma. These are the cAMP-dependent protein kinase type I and II isozymes and a "histone kinase" and a "phosvitin kinase"; neither of the latter two is regulated by cyclic nucleotides. Characterization of these enzymes was based on fractionation by DE 52 chromatography, substrate specificity, interaction with the protein inhibitor of cAMP-dependent protein kinases, and sucrose gradient sedimentation rates. Both the cAMP-dependent protein phosphotransferase activity and the phosvitin phosphotransferase activity are 2-to 4-fold elevated in the lymphosarcoma cells in comparison to thymocytes. cAMP binding is associated with both the type I and II isozymes and with a fraction tentatively designated as the regulatory subunit of these enzymes. cGMP also binds to this later fraction and to the partially purified fraction containing the type IcAMP-dependent enzyme. The histone phosphotransferase activity of this fraction is also stimulated by cGMP, but studies of the number of binding sites and of absorption to cAMP and cGMP affinity resins indicated that this fraction contains more than one species of cyclic nucleotide-binding protein.

Topics: Animals; Binding Sites; Cell Division; Cyclic AMP; Cyclic GMP; Epinephrine; Lymphoma, Non-Hodgkin; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Prostaglandins; Protein Binding; Protein Kinases; T-Lymphocytes