Effects of insulin, glucagon and triiodothyronine on DNA synthesis in rat hepatocyte primary cultures induced by liver tumour promoters and EGF

Toxicology in Vitro : an International Journal Published in Association with BIBRA
W ParzefallR Schulte-Hermann

Abstract

Enhanced cell proliferation may favour DNA-damaging processes (tumour initiation) as well as the expansion of clones of altered cells (tumour promotion). The latter process appears to be responsible for carcinogenesis by non-genotoxic compounds. We previously have established rat hepatocyte primary cultures under serum-free conditions and studied the effect of the rat liver tumour promoter cyproterone acetate (CPA) on DNA synthesis. It was found that glucocorticoid concentration of 100 nm dexamethasone was necessary for the induction of DNA synthesis. In the present study the growth supporting effect of insulin, glucagon and triiodothyronine (T3) were examined. Pretested concentrations of CPA, pregnenolone-16alpha-carbonitrile (PCN), alpha-hexachlorocyclohexane (HCH), nafenopin (NAF) and phenobarbital (PB) were added for stimulation of DNA synthesis. EGF served as a reference stimulator. Beginning with standard medium concentrations of insulin (7 nM), glucagon (0.4 nM) and triiodothyronine (100 nM) dose-response studies were obtained by leaving all but one of the hormone concentrations constant. DNA synthesis was measured by incorporation of [(3)H]thymidine into DNA. In solvent-treated dimethyl sulfoxide (DMSO) cultures insulin...Continue Reading

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Citations

Dec 30, 2015·Regulatory Toxicology and Pharmacology : RTP·Ann E BradleyJudi L Durda
Jan 20, 2004·Critical Reviews in Toxicology·James E KlaunigPenelope A Fenner-Crisp
Jan 24, 2007·Physiological Reviews·Karen Bedard, Karl-Heinz Krause

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