Sensitive detection of growth stimulating tumour promoters in perifused primary rat hepatocyte cultures

Toxicology in Vitro : an International Journal Published in Association with BIBRA
S Klein, R Gebhardt

Abstract

Comparison of stationary cultivation with discrete changes of the medium with perifusion, where the hepatocytes are cultivated under a continuous flow of medium showed an enhanced sensitivity of perifused hepatocytes towards the mitogen cyproterone acetate (CPA) and the potential tumour promoters lindane, 4-chloro-1-naphthol, dieldrin and clofibrate. Addition of these substrates significantly stimulated DNA synthesis in the perifusion cultures while stationary cultures remained dormant or reacted in a less pronounced manner. In contrast, 1-methyl-3-nitro-1-nitroso-guanidine (MNNG) at 5 mum showed no effect on the incorporation of bromodeoxyuridine (BrdU) in both systems. The increase in sensitivity may be due to physical (establishment of steady-state concentrations) and physiological advantages (enhanced biotransformation, intact signal transduction pathways) of the perifusion culture. These studies demonstrate that perifusion is more suitable than stationary rat hepatocyte cultures with respect to the detection of growth stimulatory effects of tumour promoters, as previously reported for growth inhibitory effects of some genotoxic carcinogens. Therefore, the perifusion may considerably aid in discriminating between growth inh...Continue Reading

References

May 15, 1977·Biochemical Pharmacology·W G LevineL A Stocken
May 1, 1992·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J D YarbroughJ V Thottassery
Dec 1, 1985·In Vitro Cellular & Developmental Biology : Journal of the Tissue Culture Association·W ParzefallR Schulte-Hermann
Dec 1, 1988·Experimental Cell Research·T NakamuraA Ichihara
Sep 1, 1974·CRC Critical Reviews in Toxicology·R Schulte-Hermann
Aug 1, 1995·Toxicology in Vitro : an International Journal Published in Association with BIBRA·R Gebhardt, S Fischer

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Citations

Aug 1, 1999·Toxicology in Vitro : an International Journal Published in Association with BIBRA·R GebhardtJ Doehmer
May 16, 2012·Critical Reviews in Toxicology·Edward L LeCluyseMark J Powers
Oct 3, 2008·The Journal of Bone and Joint Surgery. American Volume·Jodi SiegelPaul Tornetta

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