The extent of chromosomal aberrations induced by chemotherapy in non-human primates depends on the schedule of administration

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis 2005-06, Vol.583 (2), p.105-119
• Main Authors: Rao, V. Koneti, Knutsen, Turid, Ried, Thomas, Wangsa, Darawalee, Flynn, Bernard Mike, Langham, Gregory, Egorin, Merrill J., Cole, Diane, Balis, Frank, Steinberg, Seth M., Bates, Susan, Fojo, Tito
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chromosomal damage; CIV chemotherapy; Drug resistance; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Genotoxicity; Macaca mulatta; Medical sciences; Primates; Secondary malignancies; Toxicology
• ISSN: 1383-5718; 1879-3592
• DOI: 10.1016/j.mrgentox.2005.01.013

We utilized a non-human primate model, the rhesus monkey (Macaca mulatta), to quantitate the extent of chromosomal damage in bone marrow cells following chemotherapy. Thiotepa, etoposide, and paclitaxel were chosen as the chemotherapy agents due to their distinct mechanisms of action. Chromosomal aberrations were quantitated using traditional Giemsa stain. We sought to evaluate the extent to which genotoxicity was dependent on the schedule of administration by giving chemotherapy as either a bolus or a 96h continuous infusion. Neutropenia and areas under the concentration curve (AUCs) were monitored to ensure comparable cytotoxicity and dose administered. At least 100 metaphases were scored in each marrow sample by an investigator unaware of the treatment history of the animals. All three drugs produced a statistically significant higher percentage of abnormal metaphases following bolus chemotherapy (p