The involvement of arachidonate metabolism in the induction of rat hepatic ornithine decarboxylase (ODC) activity by the tumor promoters 12-O-tetradecanoylphorbol-13-acetate (TPA) and phenobarbital (PB) was investigated. Pretreatment of the rats with indomethacin or 5,8,11,14-eicosatetraynoic acid dose dependently inhibited the induction of ODC by both tumor promoters. Both inhibitors were more potent inhibitors of PB induction than TPA induction of ODC. The data are consistent with an involvement of arachidonate cyclooxygenase products in the induction of rat hepatic ODC by the tumor promoters.

SUMMARYIntraperitoneal injection of the non-phorbol tumor promoter anthralin (l,%dihydroxy-9-anthrone) in male rats resulted in an increase of hepatic ornithine decarboxylase (ODC) activity. Maximal activity was observed 8 h after promoter administration reaching levels about 30 times over control. The kinetics of anthralin dependent ODC induction differed markedly from that by either 12-0-tetradecanoylphorbol-13-acetate (TPA) or phenobarbital (PB) (Bisschop et al., Carcinogenesis 2 (1981) 1282). With anthralin a slow decrease of ODC back to control level is observed approximately within 22 h. In contrast, ODC induction mediated by other tumor promoters like TPA and PB decreased to control levels within 4-6 hours. Administration of a second dose of anthralin 8 h after the first dose prevented the activity decrease as normally observed after a single dose of a tumor promoter. This effect lasted at least 10 h. ODC activity induction occurred in a dosedependent manner being linear from 10-2000 pg anthralin/kg body wt. Pretreatment of the animals either with actinomycin D or with cycloheximide completely blocked anthralin mediated ODC induction suggesting that de novo ODC-mRNA synthesis and subsequent translation is involved in this process.

The food additives butylated hydroxytoluene, butylated hydroxyanisole and sodium cyclamate and the precursors for packaging materials acrylamide, acrylic acid, acrylonitrile and vinylpyrrolidone were investigated for their ability to induce hepatic ornithine decarboxylase (ODC) in vivo, in order to obtain indications about their possible tumour-promoting activities. It was shown that butylated hydroxyanisole, acrylonitrile, vinylpyrrolidone and acrylamide have the capacity to increase rat liver ODC activity, while butylated hydroxytoluene, acrylic acid and sodium cyclamate did not affect ODC activity.