Fig. 1. Spectral karyotyping (SKY) using human paints in rhesus monkey metaphases (42,XY). Apparent translocations at monkey chromosomes 2, 7 and 13 are due to repackaging of chromosomal contents from counterparts in human chromosomes 2, 14, 15, 21 and 22. Human chromosome 2 exists as two chromosomes (i.e. Chromosomes 9 and 15) in a rhesus monkey metaphase.

Fig. 2. Study design.

Fig. 3. Nomogram used for calculation of dose of chemotherapy agents in non-human primate models.

Fig. 4. Neutrophil counts obtained for the animals on study. (A) Neutrophil counts in the five animals receiving paclitaxel. Pre-treatment values obtained prior to the bolus administration (pre-bolus) or prior to the start of the infusion (pre-infusion) are compared with the lowest count recorded after administration of chemotherapy for that cycle (Bolus Nadir and Infusion Nadir). Nadir values bolus were 120, 107, 68, 685, and 645. Nadir values for infusion were 24, 549, 668, 1880, and 151. (B) Neutrophil counts for the group of animals receiving each drug.

Fig. 5. Area under the concentration curve (AUC) obtained for the animals on study. (A) AUCs in the five animals receiving thiotepa. Values calculated after bolus drug administration are compared with those calculated following infusional administration. (B) AUCs for the group of animals receiving each drug. The vertical line represents the mean value, while the box delineates the standard error. Each animal is identified by a different symbol.

Fig. 6. Examples of chromosomal damage scored in metaphase spreads following Giemsa staining. Arrows in the individual panels identify the different cytogenetic abnormalities. Panel A (normal); panel B (dicentric); panel C (chromatic fragment); panel D (complex aberration showing breaks and fragments); panel E (rings); panel F (multiple breakages and fragments). Representative examples of breaks, fragments, rings, gaps and complex aberrations are shown in the figure.

Fig. 7. Tabulation of percent abnormal metaphases found in the bone marrow sample from each individual animal. For each drug, the panel on the left demonstrates the results obtained when metaphases were scored in samples harvested directly after bone marrow aspiration. The panel on the right summarizes the data examining metaphases harvested from samples cultured in staphylococcal mitogen for 96 h.

Fig. 8. Comparison of abnormal metaphases tabulated both in the direct and the mitogen-stimulated samples. The statistical analysis of the results is summarized in the table at the bottom of the figure. All results were analyzed using an exact stratified Cochran-Armitage test.

Abnormal metaphases following chemotherapy exposure

Example of qualitative and quantitative aberrations seen following etoposide chemotherapy