Assessment of cyto/genotoxicity of irinotecan in v79 cells using the comet, micronucleus, and chromosome aberration assay.

Irinotecan is a topoisomerase I interactive agent, widely used in the treatment of metastatic colorectal cancer. The genotoxic effects of the maximum single dose (18 microg mL-1), recommended monotherapy dose (9 microg mL-1), and recommended combined therapy dose (4.5 microg mL-1) of irinotecan were studied on V79 cells using the comet assay, chromosome aberration assay, and micronucleus test. The cells were treated with irinotecan for 2 h or 24 h. The statistical significance of the results was determined using the one-way ANOVA test and a nonparametric Mann Whitney U test. The comet assay did not show dose-dependent or time-dependent effects. The chromosome aberration analysis showed large DNA rearrangements, i.e., chromosome exchanges. Although the exposed cultures showed a significant increase in micronucleated cells in respect to control, no dose-dependent relation was established among the treated cultures. Time-dependent effect was also not observed.