Response to an Active Vitamin D3 Metabolite of Transplantable Human Myeloid Leukemic Cell Lines in Adult Nude Mice

Abstract

Tumorigenicity of human myeloid leukemic cell lines KG-1, U937, HL-60 and K562 was studied in adult cyclophosphamide-primed nude mice (CPNM). All inocula except KG-1 consistently grew nonmet-astatic subcutaneous (sc) tumors after 3 weeks. Cytologic, immuno- and enzyme-cytochemical tests proved identity of respective tumor and cultured cells. Adenosine triphosphatase (ATPase) reactivity was limited to tumorigenie cells in vivo, while leucine aminopeptidase (LAP) was present both in cultured and tumor cells. Isoenzyme electrophoretic patterns clearly delineated each cell line, establishing clonality and confirming tumor cell origin. Antileukemic activity of an active vitamin D3 metabolite (D3M), 1,25-(0H)2D3, was assessed against leukemic sarcomas in vivo By transplantation of U937, HL-60 and K562 cells, and concomitant contralateral implantation of mini-osmotic pumps (MOP) containing 103ng/ml D3M in propylene glycol (PG). Tumor inhibition occurred in 75% of treated CPNM bearing HL-60, 50% with K562 and none with U937. Tumors proliferated in all untreated and control (MOP + PG) mice, but sarcomas in treated mice developed over 1 week later than in the others. Control and tumor- bearing D3M-treated mice died earlier than untreated mice, or treated mice without tumors, relating coincidence of tumor and PG, possibly through a metabolite of PG or a product of PG with the MOP. Tumor load was not a factor in lifespans of treated mice. Subclones of each line showed resistance to D3M activity in vivo. CPNM are useful models for study of human myeloid leukemic cells in vivo. MOP implants deliver consistent doses of antineoplastic agents and their solvents in vivo. D3M in an appropriate vehicle may be a valuable adjunctive agent for antineoplastic therapy of human myeloid leukemias.