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

Environ Mol Mutagen. 2005 Dec;46(4):253-9. doi: 10.1002/em.20154.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity
  • Callithrix / blood*
  • Cyclophosphamide / toxicity
  • Cytarabine / toxicity
  • Erythrocytes / drug effects*
  • Erythrocytes / pathology
  • Fluorouracil / toxicity
  • Humans
  • Methotrexate / toxicity
  • Micronuclei, Chromosome-Defective / drug effects*
  • Micronucleus Tests
  • Models, Animal*
  • Mutagenicity Tests
  • Mutagens / toxicity*
  • Primates / blood*

Substances

  • Antineoplastic Agents
  • Mutagens
  • Cytarabine
  • Cyclophosphamide
  • Fluorouracil
  • Methotrexate