Document Detail


Malignant transformation of human colon epithelial cells by benzo[c]phenanthrene dihydrodiolepoxides as well as 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine.
MedLine Citation:
PMID:  16137733     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HCAs) ingested with food have repeatedly been suggested to be involved in the malignant transformation of colon epithelial cells. In order to test this hypothesis, HCEC cells (SV40 large T antigen-immortalized human colon epithelial cells) were incubated with a racemic mixture of benzo[c]phenanthrene dihydrodiol epoxides (B[c]PhDE), extremely potent carcinogenic PAH metabolites in vivo, or with 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP), the N-hydroxylated metabolite of the most abundant HCA in cooked meat. First, it was shown that HCEC cells express sulfotransferase 1A1, which is needed to metabolize N-OH-PhIP to the corresponding N-sulfonyloxy derivative, the direct precursor molecule of genotoxic nitrenium ions. Thereafter, exponentially growing HCEC cells were exposed five times to 0.1 microg (0.37 nmol) B[c]PhDE/ml for 30 min or 0.72 microg (3 nmol) N-OH-PhIP/ml for 24 h. Chemically treated HCEC cells showed an enhanced saturation density and grew faster than the corresponding solvent-treated cell cultures. After five treatment cycles, HCEC(B[c]PhDE) as well as HCEC(N-OH-PhIP) cells lost cell-cell contact inhibition and started piling up and forming foci in the culture flasks. Furthermore, HCEC(B[c]PhDE) and HCEC(N-OH-PhIP) cells were injected i.m. into SCID mice. Within 6 weeks after injection, eight animals out of eight injected with HCEC(B[c]PhDE) or HCEC(N-OH-PhIP) cells developed tumors at the site of injection, thus demonstrating the high tumorigenic potential of the HCEC(B[c]PhDE) and HCEC(N-OH-PhIP) cell cultures. Taken together, we show for the first time that the abovementioned active PAH metabolites as well as N-OH-PhIP are indeed able to malignantly transform human colon epithelial cells in vitro.
Authors:
Uta Herbst; Judith Iris Fuchs; Wera Teubner; Pablo Steinberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-08-31
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  212     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-04-17     Completed Date:  2006-05-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  136-45     Citation Subset:  IM    
Affiliation:
Nutritional Toxicology, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Carcinogens / toxicity*
Cell Proliferation / drug effects
Cell Transformation, Neoplastic / drug effects*
Colon / cytology*,  drug effects,  ultrastructure
Dimethyl Sulfoxide / pharmacology
Epithelial Cells / drug effects,  physiology*,  ultrastructure
Epoxy Compounds / toxicity*
Humans
Imidazoles / toxicity*
Immunohistochemistry
Mice
Mice, SCID
Phenanthrenes / toxicity*
Pyridines / toxicity*
Chemical
Reg. No./Substance:
0/Carcinogens; 0/Epoxy Compounds; 0/Imidazoles; 0/Phenanthrenes; 0/Pyridines; 124489-20-9/2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine; 67-68-5/Dimethyl Sulfoxide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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