Inhibition of ornithine decarboxylase activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the activity of rat liver ornithine decarboxylase (ODC) were investigated. Sixteen hours after partial hepatectomy, rats that had been pretreated with TCDD for 1 week exhibited a 3- to 4-fold increase in ODC activity, while vehicle controls exhibited to 8- to 10-fold increase. This inhibition of ODC induction by TCDD was time dependent since TCDD administration at the time of partial hepatectomy did not produce inhibitory effects on the subsequent ODC induction. ODC induction after either aminophylline or dexamethasone administration, agents which act via cAMP-mediated and direct nuclear events, respectively, also was inhibited by pretreatment with TCDD. It was concluded that TCDD pretreatment decreased the ability of the liver to respond to hormonal stimulation as reflected in the attenuation of ODC induction. RNA polymerase I activity, which positively correlates with ODC activity in growth and development, decreased concomitantly with decreased induction of ODC. In unstimulated liver RNA polymerase I activity, as well as protein, DNA, and RNA levels, remained unchanged 1 week after TCDD. However, TCDD administration resulted in decreased liver concentrations of putrescine and spermidine, but not spermine. This suggests that TCDD pretreatment results in a time-dependent decrease in hormone responsivity.