Liver cell lines

Mersch-Sundermann V, Knasmuller S, Wu X, Dorroudi F, Kassie F (2004) Use of a human-derived liver cell line for the detection of cytoprotective, antigenotoxic and cogenotoxic agents. Toxicology 198 329-340... 

Clemons, J.H., L.E.J. Lee, C.R. Myers, D.G. Dixon, and N.C. Bols. 1996. Cytochrome P4501A1 induction by polychlorinated biphenyls (PCBs) in liver cell lines from rat and trout and the derivation of toxic equivalency factors. Canad. Jour. Fish. Aquat. Sci. 53 1177-1185. 

Another promising development is the enantioselective hydrolysis of various racemic xenobiotic esters in healthy and cancerous rat liver cell lines [22], This has led to the design of anticancer prodrugs selectively activated by cancerous cell lines. 

The enzyme induction properties of PBDEs have been less studied than for other structurally similar chemicals, but the existing information suggests that they can be classified as mixed-type inducers of hepatic microsomal monooxygenases (Damerud et al. 2001 de Wit 2002 Hardy 2002b). Few studies have examined the structure-induction relationships for PBDEs. Chen et al. (2001) examined the ability of 12 PBDE congeners and 3 commercial mixtures to induce EROD activity in chick and rat hepatocytes, in liver cell lines from rainbow trout, rat, and human, and in a human intestinal cell line. The number of... 

CIR, Chromosomal aberrations, rat liver cell line (RLi ) in vitro GIH, Gene mutation, human fibroblasts, diphtheria toxin resistance... 

Huuskonen, S.E., Ristola, T.E., Tuvikene, A., Hahn, M.E., Kukkonen, J.V.K. and Lindstrom-Seppa, P. (1998) Comparison of two bioassays, a fish liver cell line (PLHC-1) and a midge (Chironomus riparius), in monitoring freshwater sediments, Aquatic Toxicology 44 (1-2), 47-67. 

Roberts EA, Johnson KC, Harper PA, et al. 1990. Characterization of the Ah receptor mediating aryl hydrocarbon hydroxylase induction in the human liver cell line HepG2. Arch Biochem Biophys... 

Chlorobenzene was not mutagenic in several bacterial strains of Salmonella typhimurium or Escherichia coli and was negative in rat hepatic DNA repair assays however, it was weakly positive in a mouse micronucleus assay. Chlorobenzene induced transformation in Fischer 344 adult rat liver cell lines, but was not genotoxic to hepatocytes. In addition, it did not induce DNA repair in the rat he-patocyte primary culture DNA repair assay. 

Mannerstrom M, Toimela T, Ylikomi T, Tahti H. The combined use of human neural and liver cell lines and mouse hepatocytes improves the predictability of the neurotoxicity of selected drugs. Toxicol Lett 2006 165 195-202. 

Apparently, mammalian cells can also be used for screening different types of stressors, providing a multitude of end-points in a single assay. An excellent example is the Cat-Tox assay, which can be seen as a mammalian alternative for the Pro-Tox assay described above. Here, a series of 14 inducible promoters are fused with the cat gene in a human liver cell line (HepG2). This allows determination of a stress response fingerprint of a chemical compound (Todd et al., 1995). 

Knasmuller S, Mersch-Sundermann V, Kevekordes S, Darroudi F, Huber WW et al (2004) Use of human-derived liver cell lines for the detection of environmental and dietary genotoxicants current state of knowledge. Toxicology 198 315-328... 

Miranda, C.L., P. Collodi, X. Zhao, D.W. Barnes and D.R. Buhler. Regulation of cytochrome P450 expression in a novel liver cell line from zebrafish (Brachydanio rerio). Arch. Biochem. Biophys. 305 320-327, 1993. 

The role of xenobiotic metabolism in the cytotoxicity of an ecotoxicant to fish cell lines has been best studied with BaP, but even with this PAH the story is incomplete (Table 3). Two types of cytotoxic responses to BaP have been documented. One has been a transitory decline in metabolism, but not in cell viability, after BaP exposures of 24-48 h. This was observed in the rainbow trout liver cell lines, RTL-W1 and Rl174. Metabolism appeared necessary for this effect as the response was blocked in RTL-W1 and Rl by, respectively, the CYP1A inhibitor, a-naphthoflavone (ANF) and the prostaglandin-H-synthase inhibitor, indomethacin. BaP quinones were thought to be the BaP metabolites responsible for this effect. 

Bechtel, D.G. andL.EJ. Lee. Effects of aflatoxin B-l in a liver-cell line from rainbow trout (Oncorhynchus mykiss). Toxicol. In Vitro 8 317-328, 1994. 

Bols, N.C., K. Schirmer, E.M. Joyce, D.G. Dixon, B.M. Greenberg and J.J. Whyte. Ability of polycyclic aromatic hydrocarbons to induce 7-ethoxyresorufin-o-deethylase activity in a trout liver cell line. 

Bols, N.C., J.J. Whyte, J.H. Clemons, DJ. Tom, M. van den Heuvel and D.G. Dixon. Use of liver cell lines to develop toxic equivalency factors and to derive toxic equivalent concentrations in environmental samples. In Ecotoxicology Responses, Biomarkers and Risk Assessment, edited by J.T. Zelikoff, Fair Haven, NJ, SOS Publications, pp. 329-350, 1997. 

Clemons, J.H., D.G. Dixon and N.C. Bols. Derivation of 2,3,7,8-TCDD toxic equivalency factors (TEFs) for selected dioxins, furans and PCBs with rainbow trout and rat liver cell lines and the influence of exposure time. Chemosphere 34 1105-1119, 1997. 

Clemons, J.H., M. van den Heuvel, J.J. Stegeman, D.G. Dixon and N.C. Bols. Comparison of toxic equivalent factors for selected dioxin and furan congeners derived using fish and mammalian liver cell lines. Can. J. Fish. Aquat. Sci. 51 1577-1584, 1994. 

Henry, T.R., D.J. Nesbit, W. Heideman and R.E. Peterson. Relative potencies of polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners to induce cytochrome P4501A mRNA in a zebrafish liver cell line. Environ. Toxicol. Chem. 20 1053-1058, 2001. 

Segner, H., A. Behrens, E.M. Joyce, K. Schirmer and N.C. Bols. Transient induction of 7-ethoxyresorufin-O-deethylase (EROD) activity by medium change in the rainbow trout liver cell line, RTL-W1. Mar. Environ. Res. 50 489-493, 2000. 

A wide variety of data firom many laboratories indicates that the liver is a major source of somatomedin peptides. This has been demonstrated directly in studies of isolated perfused livers (F3, K13, MIO, P9, S9, S2I, W6), fetal (D14, R5) and adult (B25, S13) liver in organ culture, rat liver cell lines (M5, M26, S27), and primary hepatocyte cultures (K14, S22, S28). Tliese studies are supported by the observations that partial hepatectomy (U3) or liver disease (S14, T5) results in low circulating somatomedin activity. It has not always been clear, however, which members of the somatomedin family were being assayed in some of these studies, due to the broad specificity of the assays used (see Section 5). For example, whereas it has been well established that the BRL (buffalo rat liver) cell line, and fetal rat liver in organ culture (R5), produce peptides of the MSA or IGF-II family (M5, M26), it is not known whether normal adult liver produces IGF-II. Indeed, production of SM-G/IGF-I by adult liver has been demonstrated specifically in only two studies. In these, Schwander et al. (S21) found that a S-labeled product from perfused liver could be immunoprecipitated with an IGF-I antiserum, and Scott et al. (S22) used a specific SM-C/IGF-I RIA to demonstrate production of the peptide by adult hepatocytes in primary culture. In both studies, the measured hepatic production rate was calculated to be sufficient to account fully for circulating SM-C/IGF-I levels. 

M. M., Insulin-like growth factor-I (IGF-I) stimulates tyrosine kinase activity in purified receptors fiom a rat liver cell line. Biochem. Biophys. Res. Commun. 119, 6-13 (1984). 

The disadvantages of primary hepatocytes are mainly related to their inability to multiply in culture. Human liver cell lines (such as the ACTIVTox system) that retain all of the major liver metabolic pathways have been developed ACTIVTox cells are reported to be a highly selected subclone of HepG2 that has retained many of the properties of normal adult hepatocytes, including metabolic activity. If cultured in small hollow fiber devices, they offer potential for long-term interaction and secondary metabolite studies [53]. 

Hepatoma cell line BEL-7404 and normal liver cell line L-02... 

Mammal-derived TEFs underestimate the potency of planar PCB mixtures in fish. TEE values of non-ortho PCB congeners based on mortality of rainbow trout in early life stages are as much as 1000 times lower than TEFs proposed for human risk assessment. TEFs for PCBs were compared using cytochrome P4501A1 induction measured as EROD activity in a rainbow trout liver cell line and in a rat hepatoma cell line. EROD activity in trout liver cells was induced only by PCBs 77, 81, 118, and 126 under normal growth conditions, and in some cultures with PCBs 105,156, and 169. The trout TEFs were 0.023 for PCB 126, 0.064 for PCB 81,0.0034 for PCB 77,0.00016 for PCB 169, and 0.000017 for PCB 118 TEFs for PCBs 105 and 156 were <0.00003. In rat cells, however, all seven PCBs clearly induced EROD activity. It was concluded that the toxic impact of PCBs on rainbow trout is overestimated by risk assessment TEFs based on... 

Capsaicin and capcaicinoids have been shown to suppress the activity of A5 and A6 desaturases in a rat liver cell line (20). Feeding dietary soy isoflavones to rats has also had some interesting effects on LA metabolism (unpublished data). Overall, these food components can reduce the production of 2-series PG and 4-series LT. This effect may ameliorate hypersensitivity (11,13,15,17,18) and reduce carcinogenesis (6-8). 

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