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 D3 (1,25VD3) 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 1,25VD3 promoted an accumulation of cells in G1-phase, with 1,25VD3 being the most effective. For example, treatment with 10(-5) M 1,25VD3 yielded a 76.7% G1-phase accumulation as contrasted with 36.3% for controls, and associated with this G1-shift was a 97% loss in clonogeneticy. Treatment with RA gave a slightly less G1-phase accumulation (64%), which was associated with a 74% loss in clonogeneticy. It is suggested that RA and 1,25VD3 exert their cell cycle and anti-tumor effects by modulating cellular events or metabolism, or by promoting the accumulation of a quiescent cell population.
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D007939:Leukemia L1210 / Q000473:pathology*; D051379:Mice; D008811:Mice, Inbred DBA; D014212:Tretinoin / Q000494:pharmacology*
D014212:Tretinoin; D002117:Calcitriol