Document Detail

Global genomic changes induced by two-stage carcinogen exposure are precancerous alterations in non-transformed human liver epithelial THLE-3 cells.
MedLine Citation:
PMID:  16142307     Owner:  NLM     Status:  MEDLINE    
Global genomic changes, including DNA aneuploidy, may be necessary for carcinogenesis; however, such genomic changes in precancerous cells have not been studied extensively. To identify early global genotypic changes associated with precancerous lesions, a non-transformed human liver epithelial cell line, THLE-3, was treated with benzo[a]pyrene or N-methyl-N-nitro-N-nitrosoguanidine, then by 12-O-tetradecanoyl-phorbol-13-acetate, resulting in morphological transformation of cells. We examined genotypic changes of the transformed cells by laser scanning cytometry, fluorescence in situ hybridization, and comparative genomic hybridization. Transformed fusiform cells displayed tetraploidy, chromosomal instability, DNA copy number aberrations. Cells with these changes were still in the precancerous stage. However, it is suggested that these global genomic changes including tetraploidization provide cells with genetic alterations leading to cancer.
K Inomata; A Oga; S Kawauchi; T Furuya; K Sasaki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  27     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-09-05     Completed Date:  2006-01-31     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  925-31     Citation Subset:  IM    
Department of Pathology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
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MeSH Terms
Carcinogens / pharmacology*
Cell Line
Cell Transformation, Neoplastic
Chromosomes, Human, Pair 11 / genetics
Chromosomes, Human, Pair 17 / genetics
DNA / chemistry
DNA Damage
G0 Phase
G1 Phase
Gene Expression Regulation, Neoplastic*
Genome, Human*
In Situ Hybridization, Fluorescence
Laser Scanning Cytometry
Liver / pathology*
Neoplasms / metabolism
Nucleic Acid Hybridization
Tetradecanoylphorbol Acetate*
Time Factors
Reg. No./Substance:
0/Carcinogens; 16561-29-8/Tetradecanoylphorbol Acetate; 50-32-8/Benzo(a)pyrene; 70-25-7/Methylnitronitrosoguanidine; 9007-49-2/DNA

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