Spontaneous and mitomycin C‐induced micronuclei in peripheral blood reticulocytes from severely malnourished rats

Abstract

Severe malnutrition caused by deficiencies in protein, calorie, and micronutrient intake is widely distributed throughout the world and is a particular problem in developing countries. Animal models have been useful for studying the effects of malnutrition under different experimental conditions. In this study, we have evaluated the effect of malnutrition on the frequency of spontaneous and mitomycin C (MMC)-induced micronuclei in the peripheral blood of rats measured using a flow cytometric analysis technique. Neonatal rats were experimentally malnourished during lactation and assayed at weaning (21 days of age). The malnourished rats weighed 49.2% less than well-nourished controls and had lower concentrations of serum protein, triglycerides, and cholesterol. In rats not treated with MMC, the frequency of micronucleated reticulocytes (MN-RETs) was 1.6 times greater in malnourished rats than in well-nourished rats (0.48% +/- 0.16% vs. 0.31% +/- 0.09%). The mean MN-RET frequency measured 32 hr after treatment with single i.p. doses of 0.5, 0.75, or 1.0 mg/kg of MMC was 0.60 +/- 0.10 vs. 0.84 +/- 0.14, 1.21 +/- 0.52 vs. 2.36 +/- 0.47, and 2.50 +/- 0.06 vs. 4.64 +/- 1.14 for well-nourished vs. malnourished rats, respectively. Statistical comparisons indicate significant differences between the two groups of rats at all doses tested. Malnourishment and MMC treatment had no significant effects on the frequencies of RETs or micronucleated normochromatic erythrocytes. The data indicate that protein-calorie malnutrition during lactation is associated with increased frequencies of MN-RETs, which are indicative of chromosome damage. These findings suggest that malnutrition could result in greater susceptibility to environmental damage.

Micronucleated Erythrocytes in Peripheral Blood from Neonate Rats Exposed by Breastfeeding to Cyclophosphamide, Colchicine, or Cytosine-Arabinoside

“…The pups' day of birth was calculated once pregnancy was confirmed. After delivery, five newborn pups per mother were randomly selected for homogeneity among the groups and to assure appropriate offspring feeding [21, 22]; a total of 25 pups per group were analyzed.…”

Trimethoprim-sulfamethoxazole increase micronuclei formation in peripheral blood from weanling well-nourished and malnourished rats

“…Considerable variability in the percentage of RETs in the peripheral blood of rats has been reported in previous studies [Ortiz et al, 2004]. The relatively high level of RETs in both groups of rats in our study may be related to their young age (21-day-old or 3-week-old rats).…”

“…Another study has shown that spleen lymphocytes from UN rats during lactation have increased MN frequencies [Ortiz et al, 1995]. Furthermore, protein-calorie malnutrition experimentally produced during lactation increases the frequencies of spontaneous and MMC-induced MN-RETs in rat peripheral blood [Ortiz et al, 2004].…”

“…Three rats treated with single i.p. dose of 0.75, mg/kg of water-soluble mitomycin C (MMC; Sigma, St. Louis, MO) administered in saline work for positive control group (MN in RET; 3.4-fold increase), similar to previous determined in the laboratory [Ortiz et al, 2004].…”

In Vivo Genotoxicity Assays

“…In this case, comparison of the study data to the negative historical control data indicates that the statistically signifi cant result produced by the trend test is not indicative of a biologically relevant response to drug treatment. With regard to biological relevance and interpretation of results, it is also worth noting that a number of confounding factors have been demonstrated to induce increases in micronucleated erythrocytes including hypothermia [54,55] , induction of hematopoiesis [56] , and malnutrition [57] .…”