Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Benzamides / pharmacology
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Calcium / pharmacology
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Cell Cycle / drug effects
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Cell Nucleus / enzymology*
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Cells, Cultured
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DNA Replication / drug effects*
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Dimethylnitrosamine / toxicity*
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Epidermal Growth Factor / pharmacology
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Female
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Kinetics
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Liver / drug effects*
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Liver / enzymology
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Liver / pathology
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Liver / physiology
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Liver Neoplasms / chemically induced
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Liver Neoplasms / pathology
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Liver Neoplasms / physiopathology*
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Maternal-Fetal Exchange
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Mutagenesis
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Phenobarbital / pharmacology
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Poly(ADP-ribose) Polymerases / genetics*
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Poly(ADP-ribose) Polymerases / metabolism*
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Precancerous Conditions / chemically induced
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Precancerous Conditions / pathology
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Precancerous Conditions / physiopathology*
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Pregnancy
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Rats
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Rats, Inbred Strains
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Sodium Fluoride / pharmacology
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Tetradecanoylphorbol Acetate / pharmacology
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Thymidine / metabolism
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Transcription, Genetic / drug effects*
Substances
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Benzamides
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Epidermal Growth Factor
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Sodium Fluoride
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Poly(ADP-ribose) Polymerases
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Dimethylnitrosamine
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3-methoxybenzamide
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Tetradecanoylphorbol Acetate
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Calcium
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Thymidine
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Phenobarbital