Induction of Micronucleated Erythrocytes in Mouse Peripheral Blood After Cutaneous Application of 5-Fluorouracil

Zúñiga‐González, Guillermo Moisés; Torres-Bugarı́n, Olivia; Zamora‐Pérez, Ana Lourdes; Gómez‐Meda, Belinda Claudia; Ramos-Ibarra, María Luisa; Gallegos-Arreola, Patricia; Flores-García, Aurelio; López-Uribe, Apolinar

doi:10.1016/s0188-4409(02)00470-8

Cited by 22 publications

(17 citation statements)

References 21 publications

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“…Polychromatic erythrocytes counts in peripheral blood can be used to determine cytotoxicity, as these cells could be altered if the individual receives cytotoxic compounds. 36 Bone marrow toxicity can lead to decreases in PCE, and MNE production could diminish too. Because PCE do not lose their ribosomes approximately 24 h after they enter the circulation, they are stained with acridine orange, 25 colored red or orange, 37,38,12 making microscopic analysis easy.…”

Section: Discussionmentioning

confidence: 99%

Oral sildenafil citrate lacks genotoxicity and cytotoxicity in a primate model: Callithrix jacchus

et al. 2006

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Objective: To determine sildenafil citrate (SC) genotoxicity and cytotoxicity in the Callithrix jacchus.Study design: Fifteen organisms were assigned to one of three groups as follows: experimental (25 mg/kg of SC); negative control (glucose solution 5%); and positive control (3 mg/kg of cytocine arabinoside). Systemic hemodynamic changes were monitored in each animal before and after each treatment. A drop of blood was obtained before and after the treatment at 24-120 h. Smears were made and the frequency of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE) and polychromatic erythrocytes (PCE) was counted.Results: No significant differences in MNE, MNPCE and PCE were found in the group that received sildenafil and negative control. A significant increase in genotoxicity and cytotoxicity was observed in the positive control group. No changes were observed in systemic hemodynamic changes. Conclusion:The macro-dose of SC lacks genotoxic, cytotoxic or systemic hemodynamic changes effects in this species.

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Section: Discussionmentioning

confidence: 99%

Oral sildenafil citrate lacks genotoxicity and cytotoxicity in a primate model: Callithrix jacchus

et al. 2006

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“…This dose may have been too low to produce a micronucleogenic effect. In previous work, mice treated topically with 10-fold higher concentrations of 5-FU had significantly increased MNE frequencies [Zúñiga-González, et al, 2003b]. Unlike the situation with Ara-C, only a small percentage of 5-FU is metabolized to an active derivative [McVan, 1993].…”

Section: Mn Induction In the Common Marmosetmentioning

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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“…5-Fu was used as the positive control in this study because of its well-known ability to induce micronuclei [Nagae et al, 1991;Ohuchida et al, 1992; Nakamura , 1993;Stopper et al, 1994;Zúñiga-González et al, 2003b], and because it is used topically for the treatment of vaginal diseases [Maiman et al, 1999;Maneo et al, 1999;Syed et al, 2000;Bendesky et al, 2002;Dalrymple et al, 2004;Murta et al, 2005]. Although it is typically used in an ointment for human applications, we treated rats with an aqueous solution of 5-Fu to facilitate the preparation of smears for scoring micronuclei and to avoid interference from 5-Fu ointment residues.…”

Section: Resultsmentioning

confidence: 99%

Micronucleus induction by metronidazole in rat vaginal mucosa

Ornelas-Aguirre

Gómez‐Meda

Zamora‐Pérez

et al. 2006

Environ. Mol. Mutagen.

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Metronidazole (MTZ) is used for the treatment of many infectious diseases, including vaginal infections. While data indicate that MTZ is mutagenic and induces micronuclei in rodents, there is no information on the genotoxicity of MTZ in epithelial vaginal cells or cervical cells. In the present study, we have instilled MTZ into the vagina of rats and evaluated the micronucleus (MN) frequency in proestrus rat vaginal mucosal cells. The first identified proestrus before treatment was used to establish basal proestrus micronucleated cell (PMNC) frequencies. Rats then were assigned to one of five groups: a negative control, three MTZ treatment groups (30, 50, or 100 mg/kg MTZ), and a positive control treated with 2.5 mg of 5-fluorouracil (5-Fu) per rat. Following treatment for five consecutive days, vaginal cell samples were taken daily until three cycles of estrus were completed. Smears prepared from the samples were evaluated for micronuclei in proestrus cells. No differences were found between the PMNC frequencies of the negative control and the 30 and 50 mg/kg MTZ groups. The group treated with 100 mg/kg MTZ, however, had significantly elevated PMNC frequencies in the first and second proestrus samples, while 5-Fu treatment produced significant increases in PMNC frequency in the second and third proestrus. These results indicate that topical administration of relatively high concentrations of MTZ is genotoxic in rat vaginal mucosa cells.

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Induction of Micronucleated Erythrocytes in Mouse Peripheral Blood After Cutaneous Application of 5-Fluorouracil

Cited by 22 publications

References 21 publications

Oral sildenafil citrate lacks genotoxicity and cytotoxicity in a primate model: Callithrix jacchus

Oral sildenafil citrate lacks genotoxicity and cytotoxicity in a primate model: Callithrix jacchus

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

Micronucleus induction by metronidazole in rat vaginal mucosa

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