MODULATION OF GROWTH SUPPORTIVE AND ONCOGENIC PROPERTIES OF MURINE LEUKEMIA-CELLS

A leukemoid reaction occurs after inoculation of L1210 leukemic cells into recipient mice and the degree of granulocytosis is correlated wit h tumor progression. it was found that the sera of leukemic mice conta ined elevated levels of colony stimulating activity (CSA) when compare d with normal mouse sera. Media conditioned by L1210 cells in vitro (L 1210-CM) contained CSA which stimulated normal bone marrow myeloid col ony growth and an autostimulatory activity (ASA) which stimulated L121 0 cell proliferation. We studied the effects of trans-retinoic acid (R A) and 1,25 dihydroxyvitamin D3 (VD3) on the production of growth subs tances by L1210 cells. When L1210-CM was prepared in the presence of R A and VD3, the CSA and ASA were markedly inhibited. A combination of t he two agents was more effective than either agent. Mice inoculated wi th 1 x 10(5) L1210 suspension culture cells treated with either agent or both combined survived significantly longer than controls. Mice ino culated with L1210 cells treated with the two agents combined survived longest. By using antibodies, preliminary analysis of growth substanc es generated in L1210-CM showed that it contains primarily GM-CSF and M-CSF-like activities which were distinct from ASA. Combination antibo dy titer assays revealed that ASA was not significantly inhibited with anti-GM-CSF and anti-M-CSF antibodies, while CSA was inhibited by bet ween 61 and 84%. We conclude that RA and VD3 synergistically inhibit t he release of growth-enhancing substances by L1210 cells which may red uce the growth advantage of leukemic cells and the resulting leukocyto sis in lymphocytic leukemia.