| Author/Editor | Kokalj-Vokač, N | |
| Title | Hipometilacija in kromosomska nestabilnost pri transformiranih in rakastih celicah | |
| Type | monografija | |
| Place | Ljubljana | |
| Publisher | Medicinska fakulteta | |
| Publication year | 1993 | |
| Volume | str. 146 | |
| Language | slo | |
| Abstract | Hypomethylated agent azacytidine (AzaC) is known to induce uncoilinig of the pairing afecting constitutive heterochromatin of chromosomes 1,9,15,16 and Y. These regions are composed of alphoid (centromere) and classical satellite (secondary constrictions) DNA sequences. Using alphoid and classical satellite probes specific for chromosomes 1 and 16, we have performed two color fluorescent in situ hybridization FISH on lymphocytes cultured in presence of AzaC. We demonstrate that: uncoiling and pairing specifically occur in classical satellite containing regions at first cell generation; breakages also affect these regions; somatic recombinations occur between these regions and lead to translocations at the next cell generation. Another set of experiments was conducted in a lymphoblastoid cell lines established from a patients affected by ataxia telangiectasia (CH) who developed lymphoma. The same chromosome anomalies than after treatement by AzaC were spontaneously observed. Alphoid and classical satellite DNA sequences were found heavily demethylated, but uncoilings, pairings and recombinations affected only classical satellite containing regions. Elongations and associations were occasionally observed also in HSC 99 lymphoblastoid cell line established from a Fanconi anemia patient, where demethylation was not as strong as in CH cell line. In recurrent translocations between chromosome 1 and 16, occurring in tumor cells from breast cancer, both alphoid and classical satellite containing regions can be affected and hypomethylated. These results provide the first experimental evidence that changes in the methylation pattern are related to chromosome rearrangements. This mechanism may be directly involved in chromosome instability of cancer cells. | |
| Descriptors | LYMPHOCYTES AZACYTIDINE TRANSLOCATION (GENETICS) DNA PROBES TUMOR CELLS, CULTURED CELLS, CULTURED CYTOGENETICS CHROMOSOMES, HUMAN, PAIR 1 CHROMOSOMES, HUMAN, PAIR 16 BREAST NEOPLASMS FANCONI'S ANEMIA EPSTEIN-BARR VIRUS ATAXIA TELANGIECTASIA KARYOTYPING HETEROCHROMATIN |