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Genotoxicity of irinotecan in human lymphocytes assessed using the cytokinesis-block micronucleus assay in vitro

Irinotecan is a promising antitumor agent, mostly used in the treatment of metastatic colorectal cancer. In spite of widespread use, its cytogenetic effects were not extensively studied. The objective of present study was to evaluate the level of genetic changes in human lymphocytes exposed to two therapeutic doses (180 mg/m2 and 350 mg/m2) of irinotecan in vitro. The DNA damage was estimated using cytokinesis-block micronucleus (CBMN) assay. The frequencies of micronuclei (MN), nuclear buds, nucleoplasmic bridges as well as apoptotic morphological changes in fixed cells were studied simultaneously. Moreover, nuclear division index both in treated and control cells was estimated. The results show that irinotecan induced marked genetic changes, especially increased incidence of MN and nuclear buds as compared to untreated control. Genotoxic effects of irinotecan on lymphocytes were dose-dependent. Both concentrations caused a significant increase in the fraction of apoptotic cells. Irinotecan also induced cytotoxicity as measured by nuclear division index. Based on the results obtained we can conclude that both therapeutic concentrations of irinotecan are geno/cytotoxic to human non-target cells. Our results also point to the importance of biomarker studies in non-target cells of cancer patients after successful chemotherapy since they could be a good predictive factor to detect subpopulations of patients with genome instability.

irinotecan; human lymphocytes; in vitro; micronucleus assay

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