retinol-acetate and Leukemia-P388

Vitamin A has been shown to potentiate the cytotoxic action of anticancer agents like vincristine (VCR) against drug resistant mouse P388 leukaemia cells. In vitro tests showed enhancement by retinyl acetate of cytocidal activities of VCR against drug-sensitive leukaemia (P388/S) and VCR-resistant leukaemia (P388/VCR) cells in culture; retinyl acetate rather specifically potentiated VCR against cultured P388/VCR cells than P388/S cells. The cellular accumulation of radioactive VCR was significantly enhanced in cultured P388/VCR cells when retinyl acetate was present. The efflux of VCR from drug-resistant cells was blocked by retinyl acetate. The effect of the combination of vitamin A and VCR was also tested in vivo on the life-span of mice bearing P388/S or P388/VCR. Intraperitoneal administration of retinyl palmitate at 41.75 or 83.5 mg kg-1 was effective to potentiate the antileukaemic activity of VCR against P388/S bearing mice, and it also overcame vincristine-resistance in P388/VCR bearing mice.

Topics: Animals; Cell Survival; Colony-Forming Units Assay; Diterpenes; Drug Resistance; Drug Synergism; Leukemia P388; Leukemia, Experimental; Mice; Retinyl Esters; Time Factors; Vincristine; Vitamin A

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