Low persistence of radiation-induced centromere positive and negative micronuclei in cultured human cells.
The micronucleus (MN) assay is widely used both in genetic toxicology and in the biomonitoring of human populations. Lymphocytes, cell lines, and bone marrow and epithelial cells are usually employed as target systems in such studies. However, little effort has been done to assess the persistence of MN in highly proliferative cells. To study the behaviour of MN containing whole chromosomes or acentric fragments, we have performed a time course experiment on the persistence of gamma-ray (3 Gy) induced MN in a human lymphoblastoid cell line. The frequency and content of MN were analyzed 1, 3, 7, 14, and 56 days after irradiation by pancentromeric fluorescence in situ hybridization (FISH). We observed a clear induction of both centromere positive and negative MN at completion of the first mitotic division. The frequency of both types of MN drastically declined to basal levels 7 days after irradiation with an identical kinetics. We therefore conclude that centromere positive and negative MN are highly unstable upon cell division, indicating that the MN assay could not be a good biomarker of DNA damage induced by acute treatments in highly proliferative cells. The implication of our findings in biomonitoring and in genotoxicity studies is discussed.
Ramírez
M J
MJ
Grup de Mutagènesi, Unitat de Genètica, Departament de Genètica i de Microbiologia, Edifici Cn, Universitat Autònoma de Barcelona, 08193 Bellaterra, Cerdanyola del Vallès, Spain.
Surrallés
J
J
Puerto
S
S
Creus
A
A
Marcos
R
R
D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002503:Centromere / Q000235:genetics / Q000528:radiation effects*; D004249:DNA Damage / Q000235:genetics; D005720:Gamma Rays / Q000009:adverse effects*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D048629:Micronuclei, Chromosome-Defective / Q000235:genetics / Q000528:radiation effects*; D013997:Time Factors
D015415:Biomarkers