Abstract
Objective:
To investigate the relationship between topoisomerase II inhibitors and t(8;21) chromosomal translocation.
Methods:
The rearrangements of AML1 and ETO genes were detected by Southern Blot and the AML1-ETO fusion gene by nested RT-PCR combined with sequencing in K562 cells treated with etoposide (Vp16) and doxorubicin (DOX).
Results:
The rearrangements of AML1 gene were detectable after DOX treatment at concentrations of 10, 50 and 100 micro mol/L for 16 h, AML1-ETO fusion gene appeared after 50 micro mol/L DOX treatment for 48 h.
Conclusion:
Induction of AML1 gene rearrangement and fusion by topoisomerase II inhibitors, represents one of the molecular mechanisms of t(8;21) chromosomal translocation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Base Sequence
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Blotting, Southern
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Cell Survival / drug effects
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Core Binding Factor Alpha 2 Subunit
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DNA, Neoplasm / genetics
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DNA-Binding Proteins / genetics*
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Doxorubicin / pharmacology*
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Etoposide / pharmacology*
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Gene Rearrangement / drug effects*
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HL-60 Cells
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Humans
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K562 Cells
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Molecular Sequence Data
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Oncogene Proteins, Fusion / genetics*
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Proto-Oncogene Proteins / genetics*
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RNA, Neoplasm / genetics
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RUNX1 Translocation Partner 1 Protein
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Homology, Nucleic Acid
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Topoisomerase II Inhibitors
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Transcription Factors / genetics*
Substances
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AML1-ETO fusion protein, human
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Core Binding Factor Alpha 2 Subunit
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DNA, Neoplasm
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DNA-Binding Proteins
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Oncogene Proteins, Fusion
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Proto-Oncogene Proteins
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RNA, Neoplasm
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RUNX1 Translocation Partner 1 Protein
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RUNX1 protein, human
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Topoisomerase II Inhibitors
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Transcription Factors
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Etoposide
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Doxorubicin