The exposure of carcinogen-initiated primary neonatal rat hepatocytes to tumor promoters modulates both the transcripts and the enzymatic activity of nuclear poly(ADP-ribose) polymerase.
Four tumor promoters, i.e. PB, TPA, NAF, and DDT, added singly to a calcium-deprived synthetic medium, elicited early and late mitogenic effects and concurrent surges of nuclear poly(ADP-ribose) polymerase (pADPRP) activity in primary neonatal rat hepatocytes mutagenized with an intra-uterine dose of DMN. These actions were fully abated by the pADPRP inhibitor 3-MBA. Conversely, EGF only acted as a full mitogen when medium's calcium was at physiological levels, and its effects could not be blocked by 3-MBA. The same tumor promoters, but not EGF, also evoked a swift and lingering amplification of pADPRP transcripts in DMN-initiated hepatocytes kept in low-calcium medium. Hence, a coordinated modulation of both pADPRP transcripts and activity by xenobiotics is likely to be involved in the clonal expansion of early preneoplastic hepatocytes.
Armato
U
U
Institute of Anatomy & Histology, School of Medicine, University of Verona, Italy.
Testolin
L
L
Menegazzi
M
M
Menapace
L
L
Ribecco
M
M
Carcereri dePrati
A
A
Miwa
M
M
Suzuki
H
H
D000818:Animals; D000831:Animals, Newborn; D001549:Benzamides / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002467:Cell Nucleus / Q000201:enzymology*; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D004128:Dimethylnitrosamine / Q000633:toxicity*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000502:physiology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008431:Maternal-Fetal Exchange; D016296:Mutagenesis; D010634:Phenobarbital / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
D001549:Benzamides; D004815:Epidermal Growth Factor; D012969:Sodium Fluoride; D011065:Poly(ADP-ribose) Polymerases; D004128:Dimethylnitrosamine; C025159:3-methoxybenzamide; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D013936:Thymidine; D010634:Phenobarbital