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.
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页码:1 / 9
页数:9
相关论文
共 34 条
[11]   Irinotecan causes severe small intestinal damage, as well as colonic damage, in the rat with implanted breast cancer [J].
Gibson, RJ ;
Bowen, JM ;
Inglis, MRB ;
Cummins, AG ;
Keefe, DMK .
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2003, 18 (09) :1095-1100
[12]   Detection of topoisomerase inhibitor-induced DNA strand breaks and apoptosis by the alkaline comet assay [J].
Godard, T ;
Deslandes, E ;
Sichel, F ;
Poul, JM ;
Gauduchon, P .
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2002, 520 (1-2) :47-56
[13]  
Gradzka I, 1998, CELL BIOCHEM FUNCT, V16, P239
[14]   Combination of oxaliplatin and irinotecan on human colon cancer cell lines:: activity in vitro and in vivo [J].
Guichard, S ;
Arnould, S ;
Hennebelle, I ;
Bugat, R ;
Canal, P .
ANTI-CANCER DRUGS, 2001, 12 (09) :741-751
[15]   Consumption of an omega-3 fatty acids product, INCELL AAFA™, reduced side-effects of CPT-11 (irinotecan) in mice [J].
Hardman, WE ;
Moyer, MP ;
Cameron, IL .
BRITISH JOURNAL OF CANCER, 2002, 86 (06) :983-988
[16]   ON THE MECHANISM OF TOPOISOMERASE-I INHIBITION BY CAMPTOTHECIN - EVIDENCE FOR BINDING TO AN ENZYME DNA COMPLEX [J].
HERTZBERG, RP ;
CARANFA, MJ ;
HECHT, SM .
BIOCHEMISTRY, 1989, 28 (11) :4629-4638
[17]   MICRONUCLEUS INDUCTION BY CAMPTOTHECIN AND AMSACRINE IN BONE-MARROW OF MALE AND FEMALE CD-1 MICE [J].
HOLMSTROM, M ;
WINTERS, V .
MUTAGENESIS, 1992, 7 (03) :189-193
[18]  
Houghton PJ, 1998, ONCOLOGY-NY, V12, P84
[19]  
HSIANG YH, 1988, CANCER RES, V48, P1722
[20]  
HSIANG YH, 1985, J BIOL CHEM, V260, P4873