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- W2022771837 abstract "1-0-Alkyl-2-0-methyl-sn-glycero-3-phosphocholine (alkylmethoxy-GPC) exerts a highly selective cytotoxic activity towards a variety of tumor cells that is not seen in normal cells. Human promyelocytic leukemia (HL-60) cells are particularly sensitive to this cytotoxic action. In this report we show that when HL-60 cells are differentiated into a granulocytic form by dimethylsulfoxide (Me2SO)they become resistant toward the cytotoxic effects of alkylmethoxy-GPC. Also, after short-term exposures of the HL-60 cells to alkylmethoxy-GPC, the uptake of [methyl-3H]choline is inhibited in the undifferentiated cells, but not in those differentiated with Me2SO. Thus, cellular choline uptake appears to be a useful index for assessing the susceptibility of cells to the cytotoxic effects of antitumor phospholipids. [3H]Alkylmethoxy-GPC is poorly metabolized by both cell populations as is evident by the trace quantities of labeled metabolites formed; also, alkylmethoxyglycerols do not exert any cytotoxic activity toward undifferentiated cells. These results demonstrate that differences in the cytotoxic response of sensitive (undifferentiated) and resistant (differentiated) cells to alkylmethoxy-GPC are not due to differences in their ability to metabolize alkylmethoxy-GPC or to a phospholipase C-generated toxic metabolite. Instead the data support our earlier hypothesis that the antitumor action of alkylmethoxy-GPC is, at least in part, caused by an impaired transport of small molecules across the membrane of sensitive cells." @default.
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- W2022771837 date "1988-10-01" @default.
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- W2022771837 title "HL-60 cells become resistant towards antitumor ether-linked phospholipids following differentiation into a granulocytic form" @default.
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- W2022771837 doi "https://doi.org/10.1016/s0006-291x(88)80797-6" @default.
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