PMID- 18502768 OWN - NLM STAT- MEDLINE DCOM- 20081009 LR - 20080901 IS - 1464-3804 (Electronic) IS - 0267-8357 (Linking) VI - 23 IP - 5 DP - 2008 Sep TI - Characterization of chromosomes and chromosomal fragments in human lymphocyte micronuclei by telomeric and centromeric FISH. PG - 371-6 LID - 10.1093/mutage/gen027 [doi] AB - Micronuclei (MN), used as a biomarker of effect in exposure to genotoxic carcinogens, derive from chromosomes and chromosomal fragments lagging behind in anaphase. The two types of MN are usually distinguished from each other by centromeric fluorescence in situ hybridization (FISH), centromere-positive (C(+)) MN representing entire chromosomes and centromere-negative (C(-)) MN chromosomal fragments. The incorporation of various types of chromosomal fragments and chromosomes and chromatids to MN is still poorly understood. We used directly labelled pancentromeric and pantelomeric DNA probes to examine the contents of MN in cultured binucleate lymphocytes of four unexposed, healthy subjects (two men and two women) 35-56 years of age. The presence and number of telomeric and centromeric signals was evaluated in 200 MN (50 MN per subject). These data were used to estimate the proportion of MN harbouring terminal/interstitial fragments, acentric/centric fragments, chromatid-type/chromosome-type fragments and entire chromatids/chromosomes. The majority of the C(+) MN (96% in men and 86% in women) found contained telomeric (T(+)) sequences. Most of the C(+) T(+) MN had one centromere and two or one telomere signals, suggesting that single chromatids were more frequently involved in MN than both sister chromatids. Among the C(-) MN, telomere signals were found in 91% (men) and 79% (women), showing that fragments in MN were mostly terminal. Most C(-) T(+) MN had one telomere signal, indicating higher prevalence for chromatid-type than chromosome-type terminal fragments. Combined centromeric and telomeric FISH is expected to increase the sensitivity of detecting exposure-related effects, when the exposure induces specific types of MN and its effect is low. This approach could particularly have use in discriminating between MN harbouring chromatid- and chromosome-type fragments in studies of human exposure to chemical clastogens and ionizing radiation. FAU - Lindberg, Hanna K AU - Lindberg HK AD - New Technologies and Risks, Work Environment Development, Finnish Institute of Occupational Health, Topeliuksenkatu 41aA, FI-00250 Helsinki, Finland. hanna.lindberg@ttl.fi FAU - Falck, Ghita C-M AU - Falck GC FAU - Jarventaus, Hilkka AU - Jarventaus H FAU - Norppa, Hannu AU - Norppa H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080522 PL - England TA - Mutagenesis JT - Mutagenesis JID - 8707812 RN - 0 (DNA Probes) SB - IM MH - Adult MH - Centromere/*genetics MH - Chromosomes, Human/*genetics MH - DNA Probes/genetics MH - Female MH - Humans MH - In Situ Hybridization, Fluorescence/*methods MH - Lymphocytes/ultrastructure MH - Male MH - *Micronucleus Tests MH - Middle Aged MH - Telomere/*genetics EDAT- 2008/05/27 09:00 MHDA- 2008/10/10 09:00 CRDT- 2008/05/27 09:00 PHST- 2008/05/27 09:00 [pubmed] PHST- 2008/10/10 09:00 [medline] PHST- 2008/05/27 09:00 [entrez] AID - gen027 [pii] AID - 10.1093/mutage/gen027 [doi] PST - ppublish SO - Mutagenesis. 2008 Sep;23(5):371-6. doi: 10.1093/mutage/gen027. Epub 2008 May 22.