Micronucleus frequency in spleen lymphocytes from severely malnourished rats during lactation

Ortiz, Rocı́o; Cortés, Edith; González, Cristina; Pérez, L. Figuero; Betancourt, Miguel

doi:10.1002/em.2850260108

Cited by 18 publications

(13 citation statements)

References 23 publications

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“…The increases in MN-RETs observed in UN rats were in agreement with previously reported results that measured MN frequency and found that lymphocytes from UN children have increased MN frequencies in binucleate cells [Ortiz et al, 1997]. 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].…”

Section: Discussionsupporting

confidence: 91%

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

Ortiz

Medina

Cortés

et al. 2011

Environ. Mol. Mutagen.

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The combination of trimethoprim and sulfamethoxazole (TMP-SMX) is a widely used drug. In spite of this, there are few reports on its genotoxicity, and the results are controversial. Severe malnutrition is a complex condition that increases the susceptibility to infections. Consequently, drugs are extensively used in malnutrition cases. Experimental animal models have been widely used to study the effects of malnutrition. Neonatal rats were experimentally malnourished (UN) during lactation. The UN rats weighed 51.1% less than the well-nourished (WN) controls and had lower concentrations of serum protein and blood lipids. The micronucleus (MN) assay is useful for detecting chromosome damage induced by nutritional deficiencies. In vivo rodent MN assays have been widely used to screen genotoxic agents. In this study, we have evaluated the frequency of spontaneous and TMP-SMX-induced micronuclei in the peripheral blood of weanling (21 days of age) rats using a flow cytometric analysis technique. The spontaneous frequency of micronucleated reticulocytes (MN-RETs) was 2.7 times greater in the UN rats than in the WN rats. In rats that were not treated with TMP-SMX, the percentage of reticulocytes was significantly lower (41.1%) in the UN rats than the WN controls. A therapeutic dose of TMP-SMX (80 mg/kg (TMP), 400 mg/kg (SMX) for 48 hr) increased MN-RETs in the WN and in the UN rats. The data demonstrate the genotoxic effect of this drug. The results indicate that severe protein-calorie restriction and drug treatment enhance DNA damage in rat peripheral blood reticulocytes, potentially increasing the risk of negative effects on health.

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Section: Discussionsupporting

confidence: 91%

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

Ortiz

Medina

Cortés

et al. 2011

Environ. Mol. Mutagen.

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“…Notwithstanding, we (Friedrisch et al, 2008) and others (Betancourt et al, 1995;Ortiz et al, 1995) have already reported that nutrition factors can affect genomic stability either in diseased or healthy states. Antioxidant and folic acid deficiency has been extensively shown to increase DNA damage in children and adults.…”

Section: Discussionmentioning

confidence: 72%

Buccal micronucleus frequency is associated with age in Down syndrome

Ferreira

Prá²,

Martino-Roth³

et al. 2009

Genet. Mol. Res.

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ABSTRACT. Down syndrome has been linked to premature aging and genomic instability. We examined the frequency of micronucleus (MN) and binucleated cells in the oral mucosa of Down syndrome patients and healthy controls matched by age and gender, addressing the effect of age and family income. Down syndrome individuals had an increased number of MN (14.30 ± 9.35 vs 4.03 ± 1.71; P < 0.001) and binucleated cells (0.97 ± 1.3 vs 0.33 ± 0.66; P < 0.05) per 2000 cells. Micronucleus frequency of Down syndrome individuals correlated positively with age (r = 0.437; P = 0.009), and the older (≥21) Down syndrome age group (30.8 ± 8.4 years old) had about 2-fold more micronuclei (P ≤ 0.05) than did the younger group (<21). Average family income did not correlate with MN frequency in controls (r = -0.948; P = 0.183), but a borderline negative correlation was seen in DS subjects (r = -0.9484; P = 0.0516). Individuals whose average income was ten times minimum wages had about 2-fold less MN than those receiving around minimum wage. We conclude that the buccal MN assay is a useful and minimally invasive method for monitoring genetic damage in humans and could be used as a tool to evaluate ageassociated genomic instability in Down syndrome.

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“…Previous studies that have measured micronuclei found that lymphocytes from malnourished children have increased MN frequencies, analyzed in binucleate cells, and a greater susceptibility to MMC-induced damage [Ortiz et al, 1997]. Using similar methodology, spleen lymphocytes from rats malnourished during lactation had increased MN frequen- cies [Ortiz et al, 1995]. The MN assay has advantages over other methods as a measure of genotoxicity.…”

Section: Discussionmentioning

confidence: 98%

“…These studies indicate that malnutrition increases susceptibility to chromosome damage, as measured by chromosomal aberrations [Alu and Murthy, 1993], sister chromatid exchange [Ortiz et al, 1994], and micronuclei [Fenech, 1993;Ortiz et al, 1995].…”

Section: Introductionmentioning

confidence: 87%

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

Ortiz

Medina

Rodrı́guez

et al. 2004

Environ and Mol Mutagen

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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.

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Micronucleus frequency in spleen lymphocytes from severely malnourished rats during lactation

Cited by 18 publications

References 23 publications

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

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

Buccal micronucleus frequency is associated with age in Down syndrome

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

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