Liver cultures

Williams GM. 1980. Classification of genotoxic and epigenetic hepatocarcinogens using liver culture assays. Ann NY Acad Sci 349 273-282. 

Liver (cultured or freshly isolated DOC, GDOC, GCDOC, 72-81... 

Powers MJ, Domansky K, Kaazempur-Mofrad MR, Kalezi A, Capitano A, Upad-hyaya A, et al. A microfabricated array bioreactor for perfused 3D liver culture. Biotechnol Bioeng 2002 78 257-69. 

Acetaminophen In vivo mice liver, cultured rat Donnelly et ai. (1994) Hanawa... 

Williams, G.M. 1980. The detection of chemical mutagens/carcinogens by DNA repair and mutagenesis in liver cultures In Chemical Mutagens, Principles and Methods for Their Detection vol. 6, eds. F.J. deSerres, A. 

Hollaender, pp. 61-79. New York Plenum. Williams, G.M. 1980. Liver culture indicators for the detection of chemical carcinogens. In Short-Term Tests for Chemical... 

Biochemical analysis by high-pressure liquid chromatography (HPLC) and mass spectrometry (MS) enables analysis of the perfundate for metabolites of a liver cell culture or for tracer compounds used to assess the permeability of barrier organ systems. Also ELISA assays may be used to detect secretion of compounds such as albumin and urea from liver cultures. 

One of the most active inducing compounds is Lindane. It is about 100 times as active as AIA in porphyrin induction in chick embyro liver culture as well as in the increase in ALA-synthetase activity [21]. The relative activities of isomers of hexahydrohexachlorobenzene for porphyrin production, are Lindane, the y-isomer = 1, a =0.5, P = 0.3, E =0.25, 5 =0.15. These results may in part reflect the relative stability of the isomers whose structures are given by Hornstein [67b]. The hexahydrobromo derivative had no activity [67a]. 

The use of chick embryo liver culture in vitro as contrasted to induction in the whole animal permitted the inference that the inducing chemicals acted directly on the hepatic cells and not via other stimuli generated from other organs. The porphyrins formed could be seen by fluorescence microscopy to accumulate in the c)doplasm of the liver parenchyma cells and were identified mainly as coproporphyiin with some protoporphyrin [25]. However, Doss [70] found mainly protoporphyrin. This difference may depend on conditions of culture the older cultures had more coproporphyrin and uroporphyrin. The increase in porphyrins in tissue culture has been assumed to be a result of an increase in ALA-synthetase. With the aid of 13-cm-diameter petri dishes, it has been possible to grow sufficient numbers of cells and demonstrate with inducing chemicals an increase in vitro of ALA-synthetase activity of seven to ten times that of controls, in a 20-hour period [21]. 

After it had been shown in chick embryo liver culture treated with inhibitors that RNA and protein synthesis were required for induction of ALA-synthetase [24,25], these results were confirmed in whole-animal studies [77-79]. Narisawa and Kikuchi [79] were able to detect an increase of ALA-synthetase in the liver 1 to 2 hours after a single subcutaneous dose of 400 mg of ALA per kilogram. It was also shown that not only porphyrins but heme synthesis was increased in chemical porphyria. DeMatteis and Rimington [80], using 2- " C-glycine or Fe, found an increased heme labeling in the presence of the inducers sedormid, AIA, and griseofulvin. It was not determined whether total heme was increased or whether heme turnover had increased. 

In rats, ferric citrate [128], hydrocortisone, and triiodothyronine [125] do not induce but enhance the induction of inducing chemicals. Ferric citrate in chick embryo liver culture behaves similarly [67a]. 

Powers, M.J. et al. A microfabricated array bioreactor for perfused 3D liver cultures. Biotechnol. 

The Detection of Chemical Mutagens/ Carcinogens by DNA Repair and Mutagenesis in Liver Cultures... 

Long-term epithelial liver cultures maintain a significant level of aryl hydrocarbon hydroxylase. However, substantial heterogeneity in both... 

---