engleski

Genotoxic effect of irinotecan on human liver and colon tumor cells

Currently we are faced with an ever-growing number of diagnosed carcinomas with cancers that affect the digestive system having dominance. Irinotecan (CPT-11), a semisynthetic analogue of camptothecin, is one of the most important antineoplastic drugs developed in the last decades primarily for use in the chemotherapy of metastatic colorectal cancer. In this study, the cytotoxicity, genotoxicity and induction of free radicals were examined in hepatocellular carcinoma cell line (HepG2) and the human colon adenocarcinoma cell line (Caco-2) exposed to different concentrations of irinotecan during 2, 4, 24, and 48 hours. The alkaline comet assay was performed for detection of DNA damage in carcinoma cell lines, cell survival was determined by Neutral red test while free radicals were determined with 2’, 7’-dichlorofluorescein-diacetate (DCFH-DA). The obtained results show that toxicity of irinotecan increased depending on its concentration in the liver cell line, while no dependence on the concentration was demonstrated with colon cells. Also, it has been shown that the cytotoxic effect of irinotecan is associated with the induction of free radicals. With the prolongation of incubation time, the genotoxic effect of irinotecan on both treated cell lines was reached. Primary DNA damage in the investigated carcinoma cell lines was the result of the effect of irinotecan and oxidative stress caused by the exposure of cells to the action of irinotecan.

irinotecan ; in vitro assay ; genotoxicity ; cytotoxicity ; free radical induction

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