Tumor promoters, but not EGF, increase nuclear poly (ADP-ribose) polymerase gene expression in rat hepatocytes initiated in Utero with DMN and cultured after birth in low-calcium synthetic medium

From National Research Council Canada

DOIResolve DOI: https://doi.org/10.1007/978-1-4419-8718-1_13
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FormatText
TypeArticle
Journal titleADP-Ribosylation Reactions
ISBN978-1-4612-6456-9
978-1-4419-8718-1
Pages81–85
Abstract
Mixed, in vivo-in vitro,models of liver chemical carcinogenesis have been used only rarely [1,2]. Recently, we devised to utilize a new one of such mixed systems to clarify the role(s) played in the unfolding of liver malignancies by nuclear poly(ADP-ribosyl)ating reactions. Such metabolic events posttranslationally modify manifold nuclear protein species, including the enzyme itself, i.e. poly(ADP-ribose) polymerase (pADPRP), by which they are catalyzed [3]. Nuclear poly(ADP-ribosyl)ations are involved not only in DNA repair, but even in the modulation of gene expression related to normal and abnormal cell proliferation, as the occurrence of malignancy is prevented by established inhibitors of pADPRP [4,5]. An increased activity of nuclear pADPRP is indispensable for the multiplication of fully transformed hepatocytes [6,7]. Likewise, both partial hepatectomy and the administration of lead nitrate increase the activity and genetic expression of nuclear pADPRP in rat hepatocytes in vivo [8]. Previously, we showed that the activation of nuclear pADPRP played a pivotal role in the enactment of the mitogenic effects elicited by several tumor promoters administered to bona fide normal, primary neonatal rat hepatocytes [9,10]. In this communication we relate that the in utero initiation with a transplacental genotoxic carcinogen like dimethylnitrosamine (DMN) [11,12] and the in vitro postnatal promotion of the offspring’s initiated hepatocytes with divers xenobiotics [9,10] do increase the expression of the nuclear pADPRP gene.
Publication date
PublisherSpringer
LanguageEnglish
Peer reviewedYes
NPARC number23000447
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Record created2016-07-19
Record modified2016-07-19
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