Acentromeric micronuclei are increased in peripheral blood lymphocytes of untreated cancer patients.
Increased micronucleated cell rates, dicentric chromosomes, and other chromosomal damages have been reported in lymphocytes of cancer patients prior to the initiation of chemotherapy, and/or radiotherapy. The cause of these chromosomal damages in these lymphocytes remains unclear. In the present work, we investigated whether these micronuclei mainly reflect structural or numerical chromosomal aberrations by applying the cytokinesis-blocked micronucleus (CBMN) assay in combination with fluorescent in situ hybridization (FISH) of a DNA centromeric probe on blood samples of 10 untreated cancer patients (UCPs), and 10 healthy subjects (HSs). Micronucleated binucleated lymphocyte rate was significantly increased in patients (mean+/-S.D.: 19.0 per thousand +/-14.1 versus 9.2 per thousand +/-4.6 in controls). Trinucleated cytokinesis-blocked cells were not significantly higher in patients than in controls. Acentromeric, centromeric, and multicentromeric micronucleus levels were two-fold higher in patients than in controls, but the difference was significant only with acentromeric micronuclei. The percentage of micronuclei containing one or more centromeres averaged 69.2, and 71.5% in patients, and controls, respectively. The percentage of micronuclei containing several centromeres was 44.7% in patients, and 54.6% in controls. Among centromere-positive micronuclei, the percentage of micronuclei containing several centromeres averaged 59.7% in patients, and 75.4% in controls. These results indicate that genetic instability in peripheral blood lymphocytes of UCPs occurs because of enhanced chromosome breakage. However, a substantial proportion of this genetic instability occurs because of defects in chromosome segregation.
Baciuchka-Palmaro
M
M
Laboratoire de Biogénotoxicologie et Mutagenèse Environnementale (EA 1784-IFR PMSE 112), Facultés de Médecine et de Pharmacie, Université de la Méditerranée, 27 Bd Jean Moulin, 13385 Cedex 05, Marseille, France.
Orsière
T
T
Duffaud
F
F
Sari-Minodier
I
I
Pompili
J
J
Bellon
L
L
De Méo
M
M
Digue
L
L
Favre
R
R
Botta
A
A
D000328:Adult; D000368:Aged; D000782:Aneuploidy; D016022:Case-Control Studies; D002455:Cell Division / Q000235:genetics*; D002503:Centromere; D002869:Chromosome Aberrations; D004249:DNA Damage; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000235:genetics*; D015162:Micronucleus Tests / Q000379:methods*; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*