Document Detail


In vitro toxicity of 7H-dibenzo[c,g]carbazole in human liver cell lines.
MedLine Citation:
PMID:  12020596     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
T O'Brien; J Schneider; D Warshawsky; K Mitchell
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
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:
Created Date:  2002-05-21     Completed Date:  2002-11-14     Revised Date:  2009-04-10    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  235-43     Citation Subset:  IM    
Affiliation:
Department of Environmental Health, University of Cincinnati Medical Center, ML0056 Cincinnati OH 45267-0056, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / 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:
1P30-ESO6096/ES/NIEHS NIH HHS; 2R01-ESO4203/ES/NIEHS NIH HHS; 5T32-ESO7250/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
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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