Folate supplementation of cyclophosphamide‐treated mothers diminishes micronucleated erythrocytes in peripheral blood of newborn rats

Gómez‐Meda, Belinda Claudia; Zúñiga‐González, Guillermo Moisés; Zamora‐Pérez, Ana Lourdes; Ramos-Ibarra, María Luisa; Batista-González, Cecilia M.; Torres-Mendoza, Blanca Miriam

doi:10.1002/em.20037

Cited by 31 publications

(28 citation statements)

References 33 publications

(39 reference statements)

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“…Since 1996, our group has worked on identifying animal species with measurable frequencies of spontaneous micronucleated erythrocytes (MNEs) circulating in their peripheral blood [Zúñiga et al, 1996a;Zúñiga-González et al, 2000;Zúñiga-González et al, 2001a;Zúñiga-González et al, 2002], with the idea that analysis of MNE frequencies in these animals can be used as a biomonitor of exposure to genotoxic agents [Zúñiga-González et al, 1998;Zúñiga-González et al, 2001b;Gómez-Meda et al, 2004]. A highly proliferating tissue like blood is required to carry out this assay [Lähdetie, 1983;Shuilin and Baker, 1989;Schmezer et al, 1990;Torres-Bugarín et al, 1998;Zamora-Perez et al, 2004], and only a drop of blood is needed to measure micronucleus (MN) frequencies in peripheral blood, so that it is not necessary to kill the animal [Zúñiga-González et al, 1998;Zúñiga-González et al, 2001b].…”

Section: Introductionmentioning

confidence: 99%

Micronucleated erythrocyte frequencies in old and new world primates: Measurement of micronucleated erythrocyte frequencies in peripheral blood ofCallithrix jacchus as a model for evaluating genotoxicity in primates

Zúñiga‐González

Gómez‐Meda

Zamora‐Pérez

et al. 2005

Environ. Mol. Mutagen.

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Nonhuman primates are of particular relevance in evaluating the potential toxicity of drugs and environmental agents. We have used previously published information and data from the present study to establish a relationship for New World (NW) and Old World (OW) primates on the basis of the frequency of spontaneous micronucleated erythrocytes (MNEs) observed in peripheral blood. Data on spontaneous MNEs in peripheral blood from 15 species of primates, including humans, indicate that NW primates have significantly (P < 0.01) higher MNE frequencies (group mean, 9.5 +/- 7.3 MNEs/10,000 erythrocytes; range, 0.7-20.5/10,000 erythrocytes) than OW primates (group mean, 1.0 +/- 0.9 MNEs/10,000 erythrocytes; range, 0.0-2.6 MNEs/10,000 erythrocytes). Humans are believed to have developed in the OW, and human MNE frequencies were similar to those described for OW primate species. We selected the common marmoset (Callithrix jacchus), a NW primate, to determine whether therapeutic pediatric doses of Metotrexate (MTX; 2.5 mg/kg), Cyclophosphamide (CP; 5 mg/kg), Cytosine-arabinoside (Ara-C; 3 mg/kg), or 5-Fluorouracil (5-FU; 10 mg/kg), administered daily for two consecutive days, increase the frequency of micronuclei. Micronucleated polychromatic erythrocyte frequencies were increased significantly in groups receiving MTX, CP and Ara-C, while MNE frequencies were increased by the Ara-C treatment. The results of this study indicate that NW primates have higher spontaneous MNE frequencies than OW primates, and because of this, NW primates like the common marmoset, may be suitable for evaluating the genotoxicity of chemical agents.

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Section: Introductionmentioning

confidence: 99%

Micronucleated erythrocyte frequencies in old and new world primates: Measurement of micronucleated erythrocyte frequencies in peripheral blood ofCallithrix jacchus as a model for evaluating genotoxicity in primates

Zúñiga‐González

Gómez‐Meda

Zamora‐Pérez

et al. 2005

Environ. Mol. Mutagen.

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“…In addition, there is evidence that dietary folate deficiency enhances the ability of arsenic to induce micronuclei in peripheral blood of mice [McDorman et al, 2002]. In addition, protection from the induction of micronucleated erythrocytes in peripheral blood of newborn Wistar rats born to cyclophosphamide-treated mothers by folate supplementation has been reported [Gómez-Meda et al, 2004].…”

Section: Discussionmentioning

confidence: 98%

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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“…Micronucleated erythrocytes could be spontaneously produced in peripheral blood in mammals but the frequency of erythrocytes might increase when they meet any genotoxic compounds [13] . Bone marrow samples are used for MN tests in rabbits, as micronucleated erythrocytes are removed by spleen from peripheral blood [19] .…”

Section: Discussionmentioning

confidence: 99%

“…The contradictory results between blood and bone marrow comet assays are interesting. We already know that the genotoxicity in blood cells reflects long term exposure to clastogenic chemicals unlike the bone marrow genotoxicity situation [13] . It has also been suggested in the report of Vasquez [33] that the in vivo comet assay from different tissues may show varied results.…”

Section: Discussionmentioning

confidence: 99%

“…Micronuclei arise from chromosome breakage (a result of clastogenic activity) or lagging chromosomes (due to aneugenic activity) in the anaphase stage of cell division. Generally, mammals may produce spontaneously micronucleated cells at background level and their presence might increase when organisms are exposed to genotoxic compounds [13,14] . MN test can be conducted from peripheral blood samples, liver and bone marrow [15][16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

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Tavşanlarda Orta Dönem Gebelikleri Sonlandırılmasında Kullanılan Bir Progesteron Antagonisti Olan Aglepriston’un Genotoksik ve Sitotoksik Etkileri

Vatan¹,

Bağdaş²,

Çinkılıç³

et al. 2015

Kafkas Univ Vet Fak Derg

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Aglepristone is an antiprogestin using for pregnancy termination in veterinary medicine. The information about side effects of aglepristone is limited. The aim of the study was to investigate cytotoxicity and genotoxicity of aglepristone in mid-gestation pregnancy termination in rabbits. Fifteen New Zealand White rabbits were used and pregnant does were randomly divided into three groups. Group I (n=5) was treated with saline as the control. The does in group II (n=5) and group III (n=5) were treated with aglepristone (10 mg/kg) on 15 th day and 15 th -16 th days of pregnancy, respectively. The rabbits were sacrificed by guillotine 24 h after last treatment. Bone marrow and blood samples were immediately collected. Cytotoxic and genotoxic potential were tested by micronucleus and Comet assays. No genotoxicity and cytotoxicity were found in micronucleus test with single aglepristone administration. In contrast, two consecutive treatments of aglepristone showed high genotoxic and cytotoxic effects on bone marrow in animals. While comet assay of blood samples did not show any significant difference between groups; the results from comet assay of bone marrow cells showed the single injection of aglepristone did not induce any DNA damage but two injections group increased the DNA damage. Keywords: Aglepristone, Cytotoxic, Genotoxic, Micronucleus test, Comet assay Tavşanlarda Orta Dönem Gebelikleri Sonlandırılmasında Kullanılan Bir Progesteron Antagonisti Olan Aglepriston'un Genotoksik ve Sitotoksik Etkileri ÖzetAglepriston, veteriner hekimlikte gebeliklerin sonlandırılmasında kullanılan bir antiprogestindir. Aglepriston'un yan etkileri ile ilgili bilgiler sınırlıdır. Çalışmamızın amacı; orta gebelikte gebeliği sonlandırılan tavşanlarda aglepriston'un potansiyel sitotoksik ve genotoksik etkilerinin araştırılmasıdır. Çalışmada 15 Yeni Zelanda beyaz tavşanı kullanılmıştır ve gebe tavşanlar rastgele üç gruba ayrıldı. I. Grup (n=5) kontrol grubu olarak tuz çözeltisi ile muamele edildi. II. Grup (n=5) gebeliğin 15. gününde aglepriston (10 mg/kg) enjekte edilen III. Grup (n=5) ise gebeliğin 15. ve 16. günlerinde aglepristone enjekte edilen gruptu. Tavşanlar son enjeksiyonlardan 24 saat sonra giyotin ile sakrifiye edilerek hızlı bir şekilde kemik iliği ve kan örnekleri alındı. Sitotoksik ve genotoksik potansiyel mikroçekirdek ve komet yöntemleri ile araştırıldı. Tek aglepriston uygulaması ile gebeliği sonlandırılan tavşanlarda mikroçekirdek testi ile herhangi bir sitotoksik ve genotoksik etki belirlenemedi. Bunun tersine iki aglepriston uygulanan tavşanların kemik iliği hücrelerinde yüksek sitotoksik ve genotoksik etki belirlendi. Komet yönteminde kullanılan kan örneklerinde gruplar arasında bir fark belirlenemedi. Kemik iliği hücrelerinin kullanıldığı komet yönteminde tek enjeksiyon grubunda herhangi bir DNA hasarı belirlenmemesine rağmen çift enjeksiyon grubunda DNA hasarının arttığı belirlendi.

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Folate supplementation of cyclophosphamide‐treated mothers diminishes micronucleated erythrocytes in peripheral blood of newborn rats

Cited by 31 publications

References 33 publications

Micronucleated erythrocyte frequencies in old and new world primates: Measurement of micronucleated erythrocyte frequencies in peripheral blood ofCallithrix jacchus as a model for evaluating genotoxicity in primates

Micronucleated erythrocyte frequencies in old and new world primates: Measurement of micronucleated erythrocyte frequencies in peripheral blood ofCallithrix jacchus as a model for evaluating genotoxicity in primates

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

Tavşanlarda Orta Dönem Gebelikleri Sonlandırılmasında Kullanılan Bir Progesteron Antagonisti Olan Aglepriston’un Genotoksik ve Sitotoksik Etkileri

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