@article{2736dc6009c14780bdef1383e0e43492,
title = "In vivo induction of rat hepatic ornithine decarboxylase and plasminogen activator by 12-O-tetradecanoypphorbol 13-acetate",
abstract = "Rapid and substantial elevations in ornithine decarboxylase and plasminogen activator have been linked to tumor promotion in mouse epidermis and in vitro. Systemic administration of 12-O-tetradecanoylphorbol 13-acetate (TPA) rapidly increased both enzymic activities in rat liver. Pretreatment with either cycloheximide or actinomycin D attenuated both enzyme inductions. It is concluded that: (1) systemic TPA rapidly induces plasminogen activator and ornithine decarboxylase activities in rat liver; and (2) both inductions reflect de novo enzyme synthesis.",
keywords = "(Rat liver), Enzyme inducion, Ornithine decarboxylase, Phorbol ester, Plasminogen activator",
author = "Buckley, \{Arthur R.\} and Putnam, \{Charles W.\} and Russell, \{Diane H.\}",
note = "Funding Information: 24 h. Ornithine decarboxylase activity peaked at 4 h (P < 0.001), remained elevated through 8 h, and fell to control values at 12 h. It has been previously demonstrated that the induction of ornithine decarboxylase activity in vitro and in mouse epidermis after TPA requires de novo protein and RNA synthesis. To determine whether this requisite pertains to the liver in vivo, rats were pretreated with intraperitoneal cycloheximide or actinomycin D prior to intraperitoneal TPA. Inductions of hepatic plasminogen activator and ornithine decarboxylase activities after a single systemic dose of TPA were attenuated by both metabolic inhibitors. The mechanism(s) involved in tumor promotion is less well understood than that of initiation \textbackslash{}[25\textbackslash{}]. Phorbol esters are non-mutagenic and do not bind covalently to DNA, RNA or protein \textbackslash{}[26\textbackslash{}]I. nstead, exposure to TPA, acting through protein kinase C \textbackslash{}[27\textbackslash{}],r esults in a variety of biochemical responses including enzyme induction both in cell culture and in epidermal cells in vivo. Two enzymes induced by the administration of phorbol esters are ornithine decarboxylase and plasminogen activator. In the present study we examined the time course of the induction of both enzymes in rat liver after a single systemic administration of TPA. Both hepatic enzymes were induced rapidly to levels significantly elevated above control following intraperitoneal TPA administration. Plasminogen activator demonstrated peak activity at 2 and 12 h, while ornithine decarboxylase peaked at 4 and 8 h. The induction of both enzymes was abolished by pretreatment with cycloheximide or actinomycin D, indicating the requirement for de novo protein and RNA biosynthesis. This is consistent with data from cell culture systems as well as the mouse skin model that implicate new messenger RNA and protein synthesis in the induction of ornithine decarboxylase \textbackslash{}[11,12\textbackslash{}]a nd implicate a similar mechanism for plasminogen activator induction in viv.o by phorbol esters. This investigation was supported by a grant from the Veterans Administration Central office to CWP and by CA-14783 from the National Cancer Institute to DHR. The authors gratefully acknowledge Ada Puckett for excellent secretarial assistance.",
year = "1985",
month = jul,
day = "26",
doi = "10.1016/0304-4165(85)90282-X",
language = "English (US)",
volume = "841",
pages = "127--130",
journal = "BBA - General Subjects",
issn = "0304-4165",
publisher = "Elsevier B.V.",
number = "1",
}