Evolution of large extrachromosomal elements in HL-60 cells during culture and the associated phenotype alterations.
In the HL-60 sublines that were isolated after a long-term continuous culture, abnormally stained or abnormally banded regions on chromosomes replaced extrachromosomal double minutes. The c-MYC gene is amplified in these structures. We followed the c-MYC gene loci during a consecutive passage by using FISH, and have found a large extrachromosomal element (LEE) that preexisted at the earliest passage in a very small fraction of cells. No chromosomal integration of c-MYC sequences was observed in up to 225 passages. The LEEs persistently evolved during culture and were not excluded from the nucleus. In the LEE-positive cells, the spontaneous differentiation was blocked and the granulocytic differentiation that was induced by treatment with dimethyl sulfoxide was reversed by withdrawal of the drug. The c-MYC gene integration into LEEs is unlikely to lead to these phenotypes. The reversibility might be related to the reversible c-MYC down-regulation during the early phase of the drug treatment of HL-60 cells at early cell passages.
Haque
M M
MM
Life Science Group, Hiroshima University, Higashi-Hiroshima, Hiroshima, 739-8521, Japan.
Hirano
T
T
Itoh
N
N
Utiyama
H
H
D002454:Cell Differentiation / Q000235:genetics; D019143:Evolution, Molecular; D005111:Extrachromosomal Inheritance / Q000235:genetics; D018922:HL-60 Cells / Q000502:physiology*; D006801:Humans; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*
D016271:Proto-Oncogene Proteins c-myc