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Tranquillizers can block mitogenesis in 3T3 cells and induce differentiation in Friend cells

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Abstract

Compounds of diverse structure induce murine Friend erythroleukaemia (MEL) cell1 differentiation2–5. Seeking a common property6, Bernstein7 reported that the relationship between activity and octanol/water partition coefficients for inducers resembled that reported for anaesthetics7; moreover, anaesthetics inhibited induction. Since anaesthetics were known to increase membrane fluidity, they suggested that inducers might decrease it. Reporting evidence against unitary theories of anaesthesia9, Richards et al.10,11 suggested that lipophilic drugs competed, according to their individual structure, with membrane lipids for hydrophobic regions on membrane proteins. The antagonism between pairs of anaesthetics10,11, anaesthetics and inducers7,8 and pairs of inducers5, might thus be explained economically by Richards' anaesthesia model, inducers and lipophilic drugs acting by similar rather than contrary mechanisms. Lipophilic drugs should, therefore, induce differentiation. We report here that some tranquillizers do so. As reported elsewhere for classical inducers12, they also block non-differentiating 3T3 cells in pre-S. These findings may have application in cancer chemotherapy.

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Authors and Affiliations

  1. Cell Proliferation Laboratory, Imperial Cancer Research Fund, PO Box 123, Lincoln's Inn Fields, London, WC2A 3PX, UK

    G. D. Clarke & P. J. Ryan

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  1. G. D. Clarke
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  2. P. J. Ryan
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Clarke, G., Ryan, P. Tranquillizers can block mitogenesis in 3T3 cells and induce differentiation in Friend cells. Nature 287, 160–161 (1980). https://doi.org/10.1038/287160a0

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