The sphingosine content in regenerating rat liver cell nuclei was anal
yzed by high-performance liquid chromatography during RNA and DNA synt
hesis. Experimental activation of nucleic acid synthesis induced sphin
gosine accumulation in the cell nuclei. In parallel, induction of the
sphingomyelin cycle was observed, involving the activation of sphingom
yelinase and changes in sphingomyelin and ceramide contents. The inter
action of sphingosine with DNA and the influence of sphingosine on RNA
polymerases were studied in vitro to clarify the role of sphingosine
in replication and transcription. At a concentration of 10(-4) M, sphi
ngosine hindered the interaction of acridine orange with DNA and activ
ated transcription enzymes. Several alternative mechanisms for the inv
olvement of sphingosine in the regulation of nucleic acid synthesis ar
e discussed.