Regulation of growth and morphological modulation of HeLa₆₅ cells in monolayer culture by dibutyryl cyclic AMP, butyrate and their analogs

N⁶‐O²′‐Dibutyryl adenosine‐3′,5′ monophosphate (DBcAMP) markedly altered the morphology of HeLa cells by increasing average cell size with an increase in total cell protein and RNA. Such effects were not caused by adenosine 3′,5′ monophosphate (cAMP) or related nucleosides and nucleotides. Butyrate, an enzyme catalyzed hydrolysis product of DBcAMP, induced a jagged spindle shape in HeLa cells within 8 hours and then caused them to enlarge and resemble those grown with DBcAMP. These effects were specific for butyrate (C₄) and pentanoate (C₅) and were not observed with isomers, substituted analogs, or other fatty acid derivatives. These morphological effects were prevented by blocking protein synthesis or by altering the cytoskeleton with Colcemid or cytochalasin B.