Abstract
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.
Highlights
Irinotecan is a topoisomerase I interactive agent, widely used in the treatment of metastatic colorectal cancer
Positive control samples significantly differed in both parameters from samples treated with 18 μg mL-1, and 4.5 μg mL-1 of irinotecan, while from samples treated with 9 μg mL-1 of irinotecan they significantly differed only in the tail moment
Our findings indicate that therapeutic doses of irinotecan are genotoxic to V79 cells, but the effect is neither dose- nor time-dependent under the experimental conditions
Summary
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 μg mL-1), recommended monotherapy dose (9 μg mL-1), and recommended combined therapy dose (4.5 μg mL-1) of irinotecan were studied on V79 cells using the comet assay, chromosome aberration assay, and micronucleus test. Irinotecan is a semi-synthetic derivative of camptothecin, a quinoline-based alkaloid and DNA topoisomerase I inhibitor [1, 2]. It inhibits DNA cleavage and re-ligation induced by topoisomerase I [3, 4]. Irinotecan proved clastogenic in the mammalian in vitro (chromosome aberrations in Chinese hamster ovary cells) and in vivo (micronucleus test in mice) test systems [10]
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