Induction of rat hepatic ornithine decarboxylase by the tumor promotors 12-O-tetradecanoylphorbol-13-acetate and phenobarbital in vivo; effect of retinyl-acetate.

A single i.p. injection in rats of 20 microgram 12-O-tetradecanoylphorbol-13-acetate (TPA) or 100 mg phenobarbital (PB)/kg body weight resulted in a transient increase in liver ornithine decarboxylase (ODC) activity. Maximal stimulation of ODC activity was observed approximately 4 h after application of TPA and 4-6 h after treatment of PB. Six hours after TPA injection and greater than 8 h after treatment with PB the ODC activity had returned to control level. ODC activity induction occurred in a dose dependent manner, maximal stimulation was obtained with 20-100 microgram TPA and 100 mg PB/kg body weight, respectively. At higher doses the tumor promotors became increasingly inhibitory. The in vivo induction of rat liver ODC activity by TPA appeared to be under transcriptional control since administration of 2 mg actinomycin D/kg body weight or 50 mg cycloheximide/kg body weight 1 h prior to application of the tumor promotor prevented the increase of ODC activity. Furthermore the TPA-stimulated ODC induction was shown to be very sensitive to retinyl-acetate (RA). An i.p. dose of RA of 0.2 microgram/kg body weight applied 1 h before TPA inhibited ODC induction by 35%. Increasing the dose of RA to 20 microgram/kg body weight completely prevented the stimulation of ODC activity by TPA.