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

Autori
Kopjar, Nevenka ; Ramić, Snježana ; Milić, Mirta ; Pavlica, Vesna

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
PROGRAMME AND ABSTRACTS ; From Genes to Molecular Epidemiology, 36th Annual Meeting of the European Environmental Mutagen Society / Šram, Radim J. - Prag : EEMS, 2006

Skup
36th Annual Meeting of the European Environmental Mutagen Society

Mjesto i datum
Prag, Češka Republika, 02.07.2006. - 06.07.2006

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
irinotecan; human lymphocytes; in vitro; micronucleus assay

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Farmacija

POVEZANOST RADA