Syngeneic SL mice inoculated with murine myeloid leukemia cells (Ml) all died ofleukemia within 30 days. Treatment three times a week with 12.5-50 pmol per mouse of either la,25-dihydroxyvitamin D3 [la,25(OH) It is of great interest that some tumor cell lines also possess similar cytosol receptors to which la,25(OH)2D3 binds specifically (4-6). However, the biological function of la,25(OH)2D3 in tumor cells was not known until quite recently. In 1981, Colston et aL (7) (17,18), the most potent known stimulators in Ml cells, do not induce differentiation of HL-60 cells (13,19).It is known that syngeneic SL mice inoculated with MI cells all die of leukemia (20,21). The marked in vitro effects of la,25(OH)2D3 on cell growth and differentiation (8, 10, 19) led us to examine whether in vivo administration of la,25(OH)2D3 to tumor-bearing mice would decrease their leukemogenicity.In this report, we demonstrate that treatment with either la,25(OH)2D3 or la(OH)D3 considerably prolongs survival times of mice inoculated with Ml cells.
MATERIALS AND METHODSAnimals. Inbred SL strain mice were maintained as reported previously (20,21). Six-to eight-week old female mice were used for the experiments. Six-week-old female athymic nude mice with a BALB/c genetic background were supplied by CLEA Japan (Tokyo). They were housed under specific pathogen-free conditions by using Clean Racks (Sanki Kogyo, Tokyo).Inoculation with MI Cells. Ml cells, clone S1 (a clone sensitive to dexamethasone), were maintained as reported (22) 3, 6, 12, 24, or 48 hr later and their blood was collected. The blood plasma Abbreviations: Ml, a murine myeloid leukemia cell line; HL-60, a human myeloid leukemia cell line; la,25(OH)2D3, la,25-dihydroxyvitamin D3; la(OH)D3, la-hydroxyvitamin D3; 25(OH)D3, 25-hydroxyvitamin D3; 24R,25(OH)2D3, 24R,25-dihydroxyvitamin D3.¶ To whom reprint requests should be addressed.
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