Aluminum-induced micronuclei and apoptosis in human peripheral-blood lymphocytes treated during different phases of the cell cycle.
Although aluminum (Al) is responsible for the etiology of some human diseases, not much is known about the mechanisms of its genotoxic activity. The available data suggest that Al can induce DNA damage by modifying the structure of chromatin through the induction of reactive oxygen species or by damaging lysosomal membranes and liberating DNase. We treated human peripheral-blood lymphocytes with AlCl3 in the G0/G1 phase, in the S/G2 phase, and during the whole cell cycle. The aim of the study was to check if the sensitivity of lymphocytes to Al varied through the cell cycle. A high sensitivity in the S phase would point toward chromatin modification as the major source of DNA damage. Micronuclei (Mn) and apoptosis were assessed as the end points. Cells were treated with 1, 2, 5, 10, and 25 microg/mL AlCl3. Mn induced by 5 microg/mL of AlCl3 were analyzed by FISH for centromeric signal content. After all treatment schemes the frequency of Mn increased initially, but decreased at high AlCl3 concentrations. This drop of Mn frequency could be explained by a strong increase in the frequency of apoptosis. AlCl3 induced both Mn with and without centromeres. The G0/G1 phase of the cell cycle was found to be more sensitive than were the S and G2 phases. This points toward oxidative stress or liberation of DNase as the major source of DNA damage induced by Al.
Banasik
Anna
A
Department of Radiobiology and Immunology, Institute of Biology, Swietokrzyska Academy, Kielce, Poland. abanasik@pu.kielce.pl
Lankoff
Anna
A
Piskulak
Agnieszka
A
Adamowska
Katarzyna
K
Lisowska
Halina
H
Wojcik
Andrzej
A
D000535:Aluminum / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D003851:Deoxyribonucleases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D018384:Oxidative Stress
D000535:Aluminum; D003851:Deoxyribonucleases