scholarly journals Insensitivity of the in vitro cytokinesis-block micronucleus assay with human lymphocytes for the detection of DNA damage present at the start of the cell culture

Mutagenesis ◽  
2012 ◽  
Vol 27 (6) ◽  
pp. 743-747 ◽  
Author(s):  
G. Speit ◽  
R. Linsenmeyer ◽  
P. Schutz ◽  
S. Kuehner
2002 ◽  
Vol 49 (1) ◽  
pp. 145-155 ◽  
Author(s):  
Janusz Błasiak ◽  
Ewa Gloc ◽  
Mariusz Warszawski

Idarubicin is an anthracycline antibiotic used in cancer therapy. Mitoxantrone is an anthracycline analog with presumed better antineoplastic activity and lesser toxicity. Using the alkaline comet assaywe showed that the drugs at 0.01-10 microM induced DNA damage in normal human lymphocytes. The effect induced by idarubicin was more pronounced than by mitoxantrone (P < 0.001). The cells treated with mitoxantrone at 1 microM were able to repair damage to their DNA within a 30-min incubation, whereas the lymphocytes exposed to idarubicin needed 180 min. Since anthracyclines are known to produce free radicals, we checked whether reactive oxygen species might be involved in the observed DNA damage. Catalase, an enzyme inactivating hydrogen peroxide, decreased the extent of DNA damage induced by idarubicin, but did not affect the extent evoked by mitoxantrone. Lymphocytes exposed to the drugs and treated with endonuclease III or formamidopyrimidine-DNA glycosylase (Fpg), enzymes recognizing and nicking oxidized bases, displayed a higher level of DNA damage than the untreated ones. 3-Methyladenine-DNA glycosylase II (AlkA), an enzyme recognizing and nicking mainly methylated bases in DNA, increased the extent of DNA damage caused by idarubicin, but not that induced by mitoxantrone. Our results indicate that the induction of secondary malignancies should be taken into account as side effects of the two drugs. Direct strand breaks, oxidation and methylation of the DNA bases can underlie the DNA-damaging effect of idarubicin, whereas mitoxantrone can induce strand breaks and modification of the bases, including oxidation. The observed in normal lymphocytes much lesser genotoxicity of mitoxantrone compared to idarubicin should be taken into account in planning chemotherapeutic strategies.


1995 ◽  
Vol 16 (3) ◽  
pp. 507-512 ◽  
Author(s):  
P.A.E.L. Schilderman ◽  
E. Rhijnsburger ◽  
I. Zwingmann ◽  
J.C.S. Kleinjans

2014 ◽  
Vol 67 (6) ◽  
pp. 1059-1066 ◽  
Author(s):  
Dilek Akyıl ◽  
Arzu Özkara ◽  
S. Feyza Erdoğmuş ◽  
Yasin Eren ◽  
Muhsin Konuk ◽  
...  

Author(s):  
Emiliano Basso ◽  
Giulia Regazzo ◽  
Mario Fiore ◽  
Valentina Palma ◽  
Gianandrea Traversi ◽  
...  

2015 ◽  
Vol 29 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Ninoslav Djelić ◽  
Milena Radaković ◽  
Biljana Spremo-Potparević ◽  
Lada Živković ◽  
Vladan Bajić ◽  
...  
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