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Titolo:
DNA oxidative damage during differentiation of HL-60 human promyelocytic leukemia cells
Autore:
Covacci, V; Torsello, A; Palozza, P; Sgambato, A; Romano, G; Boninsegna, A; Cittadini, A; Wolf, FI;
Indirizzi:
Univ Sacred Heart, Inst Gen Pathol, Fac Med, I-00168 Rome, Italy Univ Sacred Heart Rome Italy I-00168 athol, Fac Med, I-00168 Rome, Italy Univ Sacred Heart, Giovanni XXIII Canc Res Ctr, Fac Med, I-00168 Rome, Italy Univ Sacred Heart Rome Italy I-00168 s Ctr, Fac Med, I-00168 Rome, Italy
Titolo Testata:
CHEMICAL RESEARCH IN TOXICOLOGY
fascicolo: 11, volume: 14, anno: 2001,
pagine: 1492 - 1497
SICI:
0893-228X(200111)14:11<1492:DODDDO>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
OXYRADICALS; PEROXIDASE; CATALASE; REPAIR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Wolf, FI Univ Sacred Heart, Inst Gen Pathol, Fac Med, I-00168 Rome, Italy Univ Sacred Heart Rome Italy I-00168 c Med, I-00168 Rome, Italy
Citazione:
V. Covacci et al., "DNA oxidative damage during differentiation of HL-60 human promyelocytic leukemia cells", CHEM RES T, 14(11), 2001, pp. 1492-1497

Abstract

DNA oxidative damage was measured in human promyelocytic leukemia HL-60 cells, in the same cells committed to granulocytic differentiation with dimethyl sulfoxide (DMSO) or all-trans-retinoic acid (RA) and in mature human peripheral granulocytes (HPG). DNA damage was evaluated as single strand breaks and 8-OHdG adducts, measured by single cell electrophoresis or by monoclonal antibodies, respectively. The basal levels of either marker of DNA damage were higher in undifferentiated HL-60 cells than in HPG and DMSO- or RA-differentiated cells. Treatment with H2O2 increased 8-OHdG formation in all cells, but the levels of DNA damage remained higher in undifferentiated cells as compared to the differentiated ones. Three lines of evidence suggested that the higher levels of DNA damage observed in undifferentiated cellswere at least in part attributable to a reduced detoxification of reactiveoxygen species (ROS). First, undifferentiated cells were shown to accumulate higher levels of dichlorodihydrofluorescein-detectable ROS than HPG and DMSO- or RA-differentiated cells. Second, undifferentiated HL-60 cells werecharacterized by reduced levels of GSH and lower GSH/GSSG ratios as compared to the differentiated cells. Third, pretreatment of undifferentiated HL-60 cells with antioxidants such as alpha -tocopherol or beta -carotene suppressed the elevation of ROS and the formation of 8-OHdG induced by H2O2. Further evidence for the importance of the oxidant/antioxidant balance was obtained by modulating the iron-catalyzed decomposition of H2O2 to hydroxyl radicals in undifferentiated HL-60 cells. In fact, pretreatment with FeSO4 increased the formation of 8-OHdG induced by H2O2, whereas pretreatment withthe iron chelator deferoxamine produced the opposite effect. These resultsillustrate correlations between the oxidant/antioxidant balance and DNA damage and suggest that the capability of a cell population to withstand oxidative stress and DNA damage may depend on its degree of differentiation.

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Documento generato il 05/12/20 alle ore 19:01:48