Abstract
CLONED, cultured mouse neuroblastoma cells, when grown in conditions which restrict cell division, extend neurites1–6 and increase the activity of neurotransmitter-related enzymes7–9. Treatments that can induce this differentiation include lowered serum concentrations3, prostaglandins4, phosphodiesterase inhibitors5 and analogues of cyclic-3′,5′-AMP (cyclic-AMP)6,10–11. These treatments have been proposed to act by elevating intracellular cyclic-AMP levels, but because they also inhibit cell division it has been difficult to determine whether their effects are due directly to cyclic-AMP or indirectly to inhibition of cell division12. As neurite growth and enzyme elevation occur during the interphase portion of the cell cycle (and are retarded during cell division), cyclic-AMP may simply allow differentiation by stopping the cell cycle in interphase3. The butyryl analogues of cyclic-AMP, in particular, markedly restrict cell division (ref. 10; see also Fig. 1a). Because butyrate, which can dissociate from the dibutyryl analogue of cyclic-AMP, can itself markedly inhibit cell division we reasoned that other analogues may exist which are not inhibitors of cell division but which effectively mimic the action of cyclic-AMP. We report here that 8-bromo-cyclic-3′,5′-AMP (8Br-cyclic-AMP) effects biochemical and morphological changes in the neuroblastoma clone NBD-2 (ref. 9) without concomitant inhibition of cell division.
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WAYMIRE, J., GILMER-WAYMIRE, K. & HAYCOCK, J. Cyclic-AMP-induced differentiation in neuroblastoma is independent of cell division rate. Nature 276, 194–195 (1978). https://doi.org/10.1038/276194a0
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DOI: https://doi.org/10.1038/276194a0
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