tretinoin and Leukemia-P388

The effect of vitamin A compounds on the DNA biosynthesis inhibition of murine ascites tumor models such as P388 lymphocytic leukemia, L1210 lymphoid leukemia, sarcoma 180 and Ehrlich ascites carcinoma was found to be concentration- and time-dependent. The results of the experiments carried out in vitro for 4 h measured by the extent of 3H-thymidine incorporation into the DNA of these tumor cells permit us to conclude that (a) at the given concentration and time, the metabolic role of vitamin A compounds influences the regulation of processes leading to DNA biosynthesis inhibition; (b) the effect of vitamin A is uniform irrespective of tumor cells heterogeneity; (c) vitamin A does not affect transport of thymidine, and (d) the dose-dependent increase in the inhibition of these tumor cells by vitamin A is characterized by undifferentiated morphology showing uniformity in the given tumor cell population associated with a total lack of differentiation.

Topics: Animals; Carcinoma, Ehrlich Tumor; Depression, Chemical; Diterpenes; DNA Replication; Leukemia L1210; Leukemia P388; Mice; Mice, Inbred DBA; Neoplasms, Experimental; Retinaldehyde; Retinoids; Retinyl Esters; Sarcoma 180; Tretinoin; Vitamin A

4,4'-(3,7,12,16-Tetramethyl-1,3,5,7,9,11,13,15,17-octadecanonaen-1 ,18-diyl) bis (1-ethylpyridinium) dibromide (Y-18598), a novel carotenoid analog with 1-ethylpyridine rings as terminal groups, was found to be effective against P388 leukemia which was refractory to amphotericin B and retinoic acid used as representatives of polyene-containing drugs. The life span of leukemic mice was increased by 56% over the control following administration of 2.5 mg/kg on days 1-5. Among these polyene-containing compounds, Y-18598 was the most highly cytotoxic to P388 leukemia cells in vitro.

Topics: Amphotericin B; Animals; Antineoplastic Agents; Carotenoids; Female; Glucose; Leukemia P388; Leukemia, Experimental; Macrophages; Mice; Mice, Inbred Strains; Tretinoin

1 alpha, 25-Dihydroxyvitamin D3 [1,25-(OH)2D3] was shown to induce a high phagocytic capability in the macrophage-like murine tumor cell line P388D1. Induction of phagocytic capability by 1,25-(OH)2D3 was dose-dependent in the range of 0.2 to 5.0 ng/ml, required the continuous presence of the secosteroid in culture, and was reversible. 25-Hydroxyvitamin D3 was an effective inducer only at about 500 ng/ml, while 24R,25-dihydroxyvitamin D3 was ineffective. The induction of the high phagocytic capability was neither accompanied by increased synthesis of lysozyme nor closely associated with an inhibitory effect on cellular proliferation. P388D1 cells bound (without ingestion) nonopsonized sheep erythrocytes (sheep RBC), and the binding increased in 1,25-(OH)2D3-treated cells. Fc-receptor-mediated binding of immunoglobulin G-coated sheep RBC was not modulated in 1,25-(OH)2D3-treated cells, but the cells acquired an Fc-receptor-mediated phagocytic capability that was expressed only when preformed P388D1-sheep RBC rosettes were further exposed to immunoglobulin G. Several differentiation agents of myeloid leukemia cells (including dexamethasone) were not effective in inducing the high-phagocytic phenotype, while retinoic acid was very effective. Different myeloid or macrophage-like tumors (WEHI-265, J774.2, PU-5, and WEHI-3) were variable in their response to 1,25-(OH)2D3.

Topics: Animals; Calcifediol; Calcitriol; Cell Differentiation; Dexamethasone; Dimethyl Sulfoxide; Leukemia P388; Leukemia, Experimental; Macrophages; Mice; Mice, Inbred BALB C; Phagocytosis; Tetradecanoylphorbol Acetate; Tretinoin