Specific induction of uncoiling and recombination by azacytidine in classical satellite-containing constitutive heterochromatin.
Azacytidine (ACR) is known to induce uncoiling and somatic association involving the constitutive heterochromatin of human chromosomes 1, 9, 15, and 16 and the Y. These regions are composed of alphoid and classical satellite DNA sequences. Using specific probes for chromosomes 1 and 16, we have performed two-color fluorescence in situ hybridization on human lymphocytes cultured in the presence of ACR. We demonstrate that for these two chromosomes (1) uncoiling and association specifically occur in classical satellite-containing regions at the first cell generation, (2) breakages also affect these regions, and (3) somatic recombinations occur between these regions and lead to translocations at the next cell generation. These results suggest that changes in methylation of repetitive DNA sequences are related to chromosomal instability occurring during cell transformation and tumorigenesis.
Kokalj-Vokac
N
N
CNRS URA 620, Institut Curie, Section de Biologie, Paris, France.
Almeida
A
A
Viegas-Péquignot
E
E
Jeanpierre
M
M
Malfoy
B
B
Dutrillaux
B
B
D001374:Azacitidine / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002878:Chromosomes, Human, Pair 1; D002885:Chromosomes, Human, Pair 16; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004276:DNA, Satellite / Q000187:drug effects*; D006570:Heterochromatin / Q000187:drug effects*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes; D008745:Methylation; D009691:Nucleic Acid Denaturation
D004276:DNA, Satellite; D006570:Heterochromatin; D004247:DNA; D001374:Azacitidine