PMID- 15162053 OWN - NLM STAT- MEDLINE DCOM- 20041101 LR - 20131121 IS - 1424-859X (Electronic) IS - 1424-8581 (Linking) VI - 104 IP - 1-4 DP - 2004 TI - Region-specific chromatin decondensation and micronucleus formation induced by 5-azacytidine in human TIG-7 cells. PG - 289-94 AB - A human diploid lung fibroblast cell strain, TIG-7, has a heteromorphic chromosome 15 with an extra short arm carrying a homogeneously staining region (15p+hsr). We demonstrated previously that the 15p+hsr consists of an inactive and G+C-rich rDNA cluster characterized by fluorescence in situ hybridization (FISH) and various chromosome banding techniques. Thus, it was suggested that the region could contain highly methylated DNA. To observe methylation status on the target region directly under the microscope, we used a demethylating agent, 5-azacytidine (5-azaC), to induce decondensation of the chromatin containing methylated DNA. At 24 h after treatment with 0.5 microM 5-azaC, marked decondensation of the 15p+hsr was observed in almost all of the metaphases. Furthermore, we observed micronuclei, which were equivalent to the rDNA of the 15p+hsr demonstrated by FISH in the same preparation. In contrast, the DNA cross-linking agent mitomycin C (MMC) preferentially induced 15p+hsr-negative micronuclei. These findings indicated that chromatin decondensation and subsequent DNA strand breakage induced by the demethylating effect of 5-azaC led specifically to 15p+hsr-positive micronuclei. CI - Copyright 2003 S. Karger AG, Basel FAU - Satoh, T AU - Satoh T AD - Genome Medical Business Division, Olympus Corporation, Hachioji, Japan. ta_sato@ot.olympus.co.jp FAU - Yamamoto, K AU - Yamamoto K FAU - Miura, K F AU - Miura KF FAU - Sofuni, T AU - Sofuni T LA - eng PT - Comparative Study PT - Journal Article PL - Switzerland TA - Cytogenet Genome Res JT - Cytogenetic and genome research JID - 101142708 RN - 0 (Chromatin) RN - 0 (Cross-Linking Reagents) RN - 0 (DNA, Ribosomal) RN - 0 (DNA, Satellite) RN - 0 (Heterochromatin) RN - 50SG953SK6 (Mitomycin) RN - M801H13NRU (Azacitidine) SB - IM MH - Azacitidine/*pharmacology/toxicity MH - Cells, Cultured/drug effects/ultrastructure MH - Chromatin/*drug effects/ultrastructure MH - Chromosome Breakage MH - Chromosomes, Human, Pair 15/*drug effects/genetics/ultrastructure MH - Cross-Linking Reagents/pharmacology/toxicity MH - DNA Damage MH - DNA Methylation/drug effects MH - DNA, Ribosomal/drug effects MH - DNA, Satellite/drug effects/ultrastructure MH - Fibroblasts/drug effects/ultrastructure MH - Heterochromatin/drug effects/ultrastructure MH - Humans MH - In Situ Hybridization, Fluorescence MH - Lung/cytology MH - Male MH - Micronucleus Tests MH - Mitomycin/pharmacology/toxicity EDAT- 2004/05/27 05:00 MHDA- 2004/11/02 09:00 CRDT- 2004/05/27 05:00 PHST- 2003/09/15 00:00 [received] PHST- 2003/12/16 00:00 [accepted] PHST- 2004/05/27 05:00 [pubmed] PHST- 2004/11/02 09:00 [medline] PHST- 2004/05/27 05:00 [entrez] AID - 77504 [pii] AID - 10.1159/000077504 [doi] PST - ppublish SO - Cytogenet Genome Res. 2004;104(1-4):289-94. doi: 10.1159/000077504.