Analysis of Mitomycin C-induced micronuclei in lymphocytes from malnourished infected children

Abstract

The purpose of this study was to determine if peripheral blood lymphocytes from malnourished children with gastrointestinal or respiratory bacterial infection show increased frequencies of Mitomycin C (MMC)‐induced micronuclei as compared to well‐nourished, infected children. The results indicate that cells from malnourished, infected children had greater chromosome damage. This may indicate that such children would be more susceptible to environmental damage and malignant transformation. Micronucleus frequencies were analyzed in binucleate cells produced by the cytokinesis block method; the overall micronucleus frequency was significantly higher in binucleate cells from malnourished, infected children. The mean micronucleus frequency in MMC‐free cultures was 4.3% in malnourished infected children and 1.0% in well‐nourished infected children. In MMC‐exposed cultures the mean induced micronucleus frequency was 32.6 ± 6.1 vs. 12.9 ± 2.3; 68.6 ± 12.1 vs. 21.0 ± 5.1, and 88.1 ± 16.2 vs. 41.7 ± 5.0 for malnourished and well‐nourished children at 20, 40, and 60 ng/ml MMC, respectively. The number of binucleated cells with more than one micronucleus was also higher in malnourished, infected children at all doses tested, including cells with two micronuclei in MMC‐free cultures from malnourished, infected children. This increase was not found in peripheral blood lymphocytes from well‐nourished infected children. Environ. Mol. Mutagen. 30:363–370, 1997 © 1997 Wiley‐Liss, Inc.

Hydrogen peroxide–induced DNA damage and DNA repair in lymphocytes from malnourished children

“…It has been suggested that cells of malnourished children are more susceptible to environmental damage [Ortiz et al, 1997]. Although statistical analysis carried out in this study does not support an overall greater susceptibility in malnourished lymphocytes to DNA damage induced by peroxide, clearly these children showed the highest proportion of highly damaged cells after H 2 O 2 treatment (Fig.…”

“…Sister-chromatid exchange analyses (SCE) have provided controversial data: whereas Mutchinick et al [1979] found that SCE frequencies were similar in well-nourished and malnourished children, Murthy and Rahiman [1983] and Ortiz et al [1994] observed significantly higher SCE frequencies in children with malnutrition. The basal frequency of micronuclei was greater in PCM children than in well-nourished controls, and lymphocytes of malnourished children showed greater susceptibility to mitomycin C-induced damage [Ortiz et al, 1997]. Furthermore, increased DNA damage in malnutrition has been detected by the single-cell gel electrophoresis technique (SCGE or comet assay), although the damage was also associated with the presence of infection and drug treatments [Betancourt et al, 1995].…”

Efecto genotóxico y mutagénico de la desnutrición moderada y grave en reticulocitos y eritrocitos de rata

“…Los ensayos cometa y de MN han sido de gran utilidad y han aportado valiosa información para el entendimiento de los efectos de la DN. Se ha observado que la DN causa daño al ADN, mismo que puede estar asociado con la presencia de infecciones y tratamientos farmacológicos a los que se someten los niños que presentan DN (Betancourt et al, 1995;Ortiz et al, 1997).…”

“…Two week-old UN and WN male Han-Wistar rats were treated daily with 0, 20, or 40 mg/kg ENU for 3 consecutive days. Blood was collected from the tail vein one day before ENU treatment (Day-1) and after ENU administration on Days 7,14,21,28,35,42,49,56 and 63. Pig-a MFs were measured in RETs and RBCs as the RET CD59− and RBC CD59− frequencies.…”

“…For instance, we have observed significant increases in the micronucleus (MN) frequency in RETs from the peripheral blood of malnourished (UN) rats compared with wellnourished (WN) rats [10]. Increases in DNA damage have also been detected in the peripheral blood lymphocytes of malnourished children [13][14][15]. Although these previous experiments have focused on the measurement of DNA damage and cytogenetic endpoints, these studies indicate that malnourishment produces DNA damage in vivo and that this damage can have negative effects on the developing organism [16].…”