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

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Abstract
A single i.p. injection in rats of 20 .mu.g 12-O-tetradecanoylphorbol-13-acetate (TPA) or 100 mg phenobarbital (PB)/kg body wt resulted in a transient increase in liver ornithine decarboxylase (ODC) activity. Maximal stimulation of ODC activity was observed .apprx. 4 h after application of TPA and 4-6 h after treatment of PB. Six hours after TPA injection and > 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 .mu.g TPA and 100 mg PB/kg body wt, respectively. At higher doses the tumor promoters 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 wt or 50 mg cycloheximide/kg body wt 1 h prior to application of the tumor promoter prevented the ODC activity. The TPA-stimulated ODC induction was very sensitive to retinyl acetate (RA). An i.p. dose of RA of 0.2 .mu.g/kg body wt applied 1 h before TPA inhibited ODC induction by 35%. Increasing the dose of RA to 20 .mu.g/kg body wt completely prevented the stimulation of ODC activity by TPA.