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

Abstract

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.

Feasibility of conducting the micronucleus test in circulating erythrocytes from different mammalian species: An anatomical perspective

“…In general, however, the results by Zúniga and colleagues Environmental and Molecular Mutagenesis. DOI 10.1002/em Cristaldi et al, 2004 agree with this present analysis [Zúñiga-Gonzalez et al, 2005]. It must be emphasised that the micronucleus test can be performed in the peripheral blood of species with spleens that remove micronuclei, as long as the test is limited to scoring micronuclei in PCEs.…”

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

“…These compounds are known to pass into breast milk [10, 24], although the transference of COL through breast milk is undefined. The following groups were formed (five rats per group), each containing a mother and five of her offspring: Group 1 (negative control), which was given sterile water; Groups 2, 3, and 4, which were given CP at 5, 10, or 20 mg/kg/day [17]; Groups 5, 6, and 7, which were given COL at 0.1, 0.2, or 0.4 mg/kg/day [25]; and Groups 8, 9, and 10, which were given AraC at 3, 4.5, or 6 mg/kg/day [26, 27], respectively. All doses administered by oral gavage were adjusted to a final volume of 0.5 mL with sterile water, and the doses administered by intramuscular administration were adjusted to a final volume of 0.2 mL with sterile water.…”

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

“…The marmoset is a recently developed non-human primate model that was chosen in the present work owing to its high spontaneous micronucleated erythrocytes (MNE) frequency and its relatively small size. 28 …”