| In vitro toxicity of 7H-dibenzo[c,g]carbazole in human liver cell lines. | |
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MedLine Citation:
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PMID: 12020596 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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7H-Dibenzo[c,g]carbazole (DBC) is a model N-heterocyclic aromatic compound (NHA) which is both a hepatotoxin and hepatocarcinogen in rodents. The focus of this investigation was to determine whether human liver cell lines display differential sensitivities to DBC-induced toxicity. Treatment of cell lines with increasing DBC concentrations produced apoptosis only in HepG2 cells. Although DBC inhibited the clonogenic growth of all cell lines at high concentrations, only the survival of HepG2 cells was reduced at lower concentrations. DBC inhibited DNA synthesis in two (HepG2, HLF) of the three cell lines at lower concentrations and was effective only at a high concentration in Mahlavu cells. Differences in DBC uptake were not observed in any of the cell lines, suggesting that bioavailability was not a limiting factor. DBC-DNA adducts were not detected in HLF or Mahlavu cells at either low or high concentrations of DBC. Consistent with the DNA adduct data, RP-HPLC analysis indicated that DBC was metabolized to a lesser degree in the HLF and Mahlavu cells. These results suggest that human liver cell lines differ markedly in the ability to metabolize DBC to toxic species and that DBC-induced apoptosis is only observed in cells that produce detectable metabolites and DBC-DNA adducts. |
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Authors:
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T O'Brien; J Schneider; D Warshawsky; K Mitchell |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Toxicology in vitro : an international journal published in association with BIBRA Volume: 16 ISSN: 0887-2333 ISO Abbreviation: Toxicol In Vitro Publication Date: 2002 Jun |
Date Detail:
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Created Date: 2002-05-21 Completed Date: 2002-11-14 Revised Date: 2009-04-10 |
Medline Journal Info:
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Nlm Unique ID: 8712158 Medline TA: Toxicol In Vitro Country: England |
Other Details:
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Languages: eng Pagination: 235-43 Citation Subset: IM |
Affiliation:
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Department of Environmental Health, University of Cincinnati Medical Center, ML0056 Cincinnati OH 45267-0056, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects Carbazoles / metabolism, toxicity* Carcinogens / metabolism, toxicity* Carcinoma, Hepatocellular Cell Survival / drug effects Chromatography, High Pressure Liquid DNA / biosynthesis DNA Adducts / biosynthesis DNA, Neoplasm / analysis Dose-Response Relationship, Drug Flow Cytometry Hepatocytes / drug effects*, metabolism, pathology Humans In Situ Nick-End Labeling Nucleic Acid Synthesis Inhibitors / metabolism, toxicity Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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1P30-ESO6096/ES/NIEHS NIH HHS; 2R01-ESO4203/ES/NIEHS NIH HHS; 5T32-ESO7250/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Carbazoles; 0/Carcinogens; 0/DNA Adducts; 0/DNA, Neoplasm; 0/Nucleic Acid Synthesis Inhibitors; 194-59-2/7H-dibenzo(c,g)carbazole; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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