Abolition of L1210 clonogeneticy and G1 arrest by retinoic acid and 1,25-dihydroxyvitamin D3

Results from this study demonstrate that L1210 lymphocytic leukemia cells generate tumor cell colonies in plasma clot culture, and that the cells can be maintained in suspension cultures for 3 days without a loss in viability or clonogeneticy. Additions of 10 −5 –10 −8 M retinoic acid (RA) or 1,25-dihydroxyvitamin D 3 (1,25VD 3 ) to suspension cultures had no effect on cell viability. However, there was an increase in cellular adherence, nuclear chromatin condensation and a depression of clonogenic potential by 99–25%. Flow cytometry analysis of 3-day suspension cultures revealed that both RA or 1,25VD 3 promoted an accumulation of cells in G 1 -phase, with 1,25VD 3 being the most effective. For example, treatment with 10 −5 M 1,25VD 3 yielded a 76.7% G 1 -phase accumulation as contrasted with 36.3% for controls, and associated with this G 1 -shift was a 97% loss in clonogeneticy. Treatment with RA gave a slightly less G 1 -phase accumulation (64%), which was associated with a 74% loss in clonogeneticy. It is suggested that RA and 1,25VD 3 exert their cell cycle and anti-tumor effects by modulating cellular events or metabolism, or by promoting the accumulation of a quiescent cell population.