Biphasic and differential effects of the cytostatic agents avarone and avarol on DNA metabolism of human and murine T and B lymphocytes.
The two novel antimitotic and potent antileukemic agents avarone and avarol were determined to inhibit the [3H]-dThd incorporation rates of both murine spleen and human peripheral blood lymphocytes within the concentration range of 2-6 microM. The mitogens concanavalin A (ConA; for T lymphocytes), lipopolysaccharide (LPS; for murine B lymphocytes) and pokeweed mitogen (PWM; for human T and B lymphocytes) were used to stimulate DNA synthesis in the lymphocyte fractions. The ED50 concentrations, causing a 50% reduction of [3H]-dThd incorporation, were significantly lower in the experiments with avarone than in those with avarol. Moreover it was established that the DNA synthesis of ConA-activated lymphocytes was more sensitively inhibited by the compounds than that of LPS or PWM-activated cells, or non-activated cells. In addition it was elucidated that at low concentrations (1-2 microM) avarone and avarol caused a stimulation of dThd incorporation only in LPS or PWM-activated lymphocytes. Based on these results it is assumed that both antileukemic agents also affect differentially the different hematologic neoplasms.
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D053138:Cyclohexenes; D004247:DNA / Q000096:biosynthesis*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D008940:Mitotic Index / Q000187:drug effects; D012717:Sesquiterpenes / Q000494:pharmacology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D053138:Cyclohexenes; D008934:Mitogens; D012717:Sesquiterpenes; C046374:avarone; D004247:DNA; C023663:avarol