engleski

Application of the alkaline comet assay to assess DNA instability in different cell types of Wistar rats exposed to irinotecan

Irinotecan (IRI) is one of the most important antineoplastic drugs used in the chemotherapy of metastatic colorectal cancer. By binding to topoisomerase I-DNA complex it prevents religation of the DNA strand, causing double-strand DNA breakage and cell death. Considering the well- established sensitivity of the alkaline comet assay for detection of DNA damage in single cells, this study aimed to clarify (I) dynamics of DNA instability in liver cells, leukocytes and brain cells of male Wistar rats that were intraperitoneally administered single IRI dose of 100 mg/kg b.w., and (II) to establish the differences between levels of DNA damage produced in the studied cell types. Outcomes of the IRI exposure were assessed at first, fourth and eight post-treatment day. Corresponding control groups of rats were studied in parallel. To establish the overall toxic effects, we also estimated changes in total body weight, liver and brain weights of experimental animals. IRI treatment diminished total body weight of rats at each time-point of interest and also affected liver and brain weights compared to controls. The highest level of primary DNA damage was detected on the fourth post- treatment day in liver and brain cells, and on the eight post-treatment day in leukocytes. Observed pattern of DNA damage could be related both to induction of lesions and their repair, which obviously created additional DNA damage detectable by the alkaline comet assay. Brain cells were the most vulnerable cell type following IRI exposure. Differences in the cell susceptibility could be also related to inherent defence mechanisms in tested tissues which has to be proven in the forthcoming studies.

irinotecan, colorectal cancer, comet assay, Wistar rats

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