Genomic instability in Down syndrome and Fanconi anemia assessed by micronucleus analysis and single-cell gel electrophoresis

Cytokinesis-block micronucleus (CB-MN) assay and single-cell gel electropho resis (SCGE) were employed to analyze leukocytes from 14 Fanconi anemia (FA ) patients, 30 Down syndrome (DS) patients, and 30 control individuals, to examine the sensitivity of these techniques to detect genomic instability i n these 2 diseases. The DS patients presented increased DNA damage as measu red by SCGE in relation to controls. The frequencies of micronuclei and dic entric bridges were similar to those of controls. Micronucleus frequency, d icentric bridge frequencies, and DNA damage were higher in FA patients than in controls. The high frequency of micronuclei observed in FA patients see ms to be due to clastogenic events, because an increase in the frequency of dicentric bridges was also observed. Micronuclei are expressed mutations a nd need cell division to appear. The damage detected by SCGE is repairable. and does not;require cell division. Under alkaline conditions, SCGE assess es double- and single-strand breaks and alkali-labile sites. The 2 methods are efficient for monitoring mutagenic events in exposed populations or in individuals with genetic instability. While the damage measured by micronuc leus analysis is accumulated over a long period of time, DNA damage measure d by SCGE reflects recent, unrepaired events. (C) 2001 Elsesvier Science In c. All rights reserved.