ASSESSMENT OF CYTO/GENOTOXICITY OF IRINOTECAN IN V79 CELLS USING THE COMET, MICRONUCLEUS, AND CHROMOSOME ABERRATION ASSAY

被引:8
作者
Kasuba, Vilena [1 ]
Rozgaj, Ruzica
Gamulin, Marija [2 ]
Trosic, Ivancica
机构
[1] Univ Zagreb, Clin Hosp Ctr Zagreb, Mutagenesis Unit, Inst Med Res & Occupat Hlth, HR-10001 Zagreb, Croatia
[2] Univ Zagreb, Oncol Clin, Zagreb, Croatia
来源
ARHIV ZA HIGIJENU RADA I TOKSIKOLOGIJU-ARCHIVES OF INDUSTRIAL HYGIENE AND TOXICOLOGY | 2010年 / 61卷 / 01期
关键词
alkaline comet assay; antineoplastic drug; cell cultures; DNA and cytogenetic damage; topoisomerase; DNA TOPOISOMERASE-I; INTESTINAL DAMAGE; ANTICANCER DRUGS; BREAST-CANCER; STRAND-BREAKS; BLOOD-CELLS; BONE-MARROW; CAMPTOTHECIN; APOPTOSIS; VITRO;
D O I
10.2478/10004-1254-61-2010-1967
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
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 mu g mL(-1)), recommended monotherapy dose (9 mu g mL(-1)), and recommended combined therapy dose (4.5 mu g 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.
引用
收藏
页码:1 / 9
页数:9
相关论文
共 34 条
[1]   MUTAGENICITY AND CARCINOGENICITY OF TOPOISOMERASE-INTERACTIVE AGENTS [J].
ANDERSON, RD ;
BERGER, NA .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 1994, 309 (01) :109-142
[2]   Molecular Cytogenetic Evaluation of the Mechanism of Micronuclei Formation Induced by Camptothecin, Topotecan, and Irinotecan [J].
Attia, Sabry M. ;
Aleisa, Abdulaziz M. ;
Bakheet, Saleh A. ;
Al-Yahya, Abdulaziz A. ;
Al-Rejaie, Salim S. ;
Ashour, Abdelkader E. ;
Al-Shabanah, Othman A. .
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, 2009, 50 (02) :145-151
[3]   Genotoxicity of two anticancer drugs, gemcitabine and topotecan, in mouse bone marrow in vivo [J].
Aydemir, N ;
Bilaloglu, R .
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2003, 537 (01) :43-51
[4]  
BACHER LC, 1990, MUTAGENESIS, V5, P541
[5]   Homocamptothecins: potent topoisomerase I inhibitors and promising anticancer drugs [J].
Bailly, C .
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2003, 45 (01) :91-108
[6]   Synergistic cytotoxicity, apoptosis and protein-linked DNA breakage by etoposide and camptothecin in human U87 glioma cells: dependence on tyrosine phosphorylation [J].
Ciesielski, MJ ;
Fenstermaker, RA .
JOURNAL OF NEURO-ONCOLOGY, 1999, 41 (03) :223-234
[7]   DNA strand-breaks induced by the topoisomerase I inhibitor camptothecin in unstimulated human white blood cells [J].
Daza, P ;
Torreblanca, J ;
García-Herdugo, G ;
Moreno, FJ .
CELL BIOLOGY INTERNATIONAL, 2002, 26 (08) :707-713
[8]   THE S-PHASE CYTOTOXICITY OF CAMPTOTHECIN [J].
DELBINO, G ;
LASSOTA, P ;
DARZYNKIEWICZ, Z .
EXPERIMENTAL CELL RESEARCH, 1991, 193 (01) :27-35
[9]  
ENG WK, 1988, MOL PHARMACOL, V34, P755
[10]   Effect of interleukin-11 on ameliorating intestinal damage after methotrexate treatment of breast cancer in rats [J].
Gibson, RJ ;
Keefe, DMK ;
Thompson, FM ;
Clarke, JM ;
Goland, GJ ;
Cummins, AG .
DIGESTIVE DISEASES AND SCIENCES, 2002, 47 (12) :2751-2757