gamma-linolenic-acid and Leukemia--Lymphocytic--Chronic--B-Cell

Gamma linolenic acid (GLA) is cytotoxic to many types of human cancer cells. Most chemotherapeutic agents are cytotoxic by inducing apoptosis. We examined the apoptotic activity of GLA on purified B-cells isolated from patients with B-cell chronic lymphocytic leukaemia (B-CLL) and from normal individuals. GLA significantly increased the degree of apoptosis in B-CLL B-cells after 24 hours of culture. The mean percentage of cells undergoing apoptosis when cultured in medium alone (spontaneous apoptosis) was 20% (range: 7 to 31%) (n=25) and in the presence of GLA (5 microg-60 microg) was: 42%-95%. In the presence of GLA 5 microg/ml and dexamethasone the degree of apoptosis was 86% (range: 72 to 100%). GLA induced apoptosis in B-CLL B-cells at a higher level than that observed with normal B-cells at all lower concentrations tested 5, 10 and 15 microg/ml: P=0.045; 0.027 and 0.022, respectively. At 30 microg/ml of GLA, no significant difference in the percentage of cells displaying apoptosis between B-CLL and normal B-cells was observed (P=0.075). GLA induced apoptosis in B-CLL T-cells at both 10 and 30 microg/ml. The degree of apoptosis in normal T-cells with GLA was also significant at the higher concentration of 30 microg/ml. Interleukin 4 (IL4), a viability factor in B-CLL, and vitamin E, an anti-oxidant, protected B-CLL B-cells against GLA (20 microg/ml)-induced apoptosis. These results demonstrate that GLA induces apoptosis in B-CLL B- and T-cells cells in vitro and that they are more susceptible to GLA-induced apoptosis than normal peripheral blood B- and T-cells.

Topics: Antibodies, Monoclonal; Apoptosis; B-Lymphocytes; Dexamethasone; Dose-Response Relationship, Drug; Drug Interactions; Flow Cytometry; gamma-Linolenic Acid; Humans; Interleukin-4; Leukemia, Lymphocytic, Chronic, B-Cell; Recombinant Proteins; T-Lymphocytes; Tumor Cells, Cultured; Vitamin E

Lymphomas developed in mice treated with X-irradiation. The radiosensitivity of cells of the lymphomas had a bimodal frequency distribution. The cells of 11 lymphomas had approximately the same radiosensitivity as normal murine lymphocytes; 6 lymphomas were highly radioresistant. Radioresistant and radiosensitive lymphomas were analogous to intractable chronic lymphocytic leukemia (CLL) and to responsive CLL in humans. The radioresistant lymphomas can be used to study the effect of therapeutic agents on the animal model for intractable CLL both in vitro and in vivo.

Topics: Animals; Disease Models, Animal; gamma-Linolenic Acid; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Linolenic Acids; Lymphoma; Mice; Radiation Tolerance