Global genomic changes induced by two-stage carcinogen exposure are precancerous alterations in non-transformed human liver epithelial THLE-3 cells.
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.
Inomata
K
K
Department of Pathology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Oga
A
A
Kawauchi
S
S
Furuya
T
T
Sasaki
K
K
D001564:Benzo(a)pyrene; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004247:DNA / Q000737:chemistry; D004249:DNA Damage; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D047569:Laser Scanning Cytometry; D008099:Liver / Q000473:pathology*; D008769:Methylnitronitrosoguanidine; D009369:Neoplasms / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D011003:Ploidies; D016192:Resting Phase, Cell Cycle; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors
D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; D001564:Benzo(a)pyrene; D004247:DNA; D013755:Tetradecanoylphorbol Acetate