Genotoxicity of two anticancer drugs, gemcitabine and topotecan, in mouse bone marrow in vivo

Çinkılıç, Nilüfer; Bilaloĝlu, Rahmi

doi:10.1016/s1383-5718(03)00049-4

Cited by 81 publications

(55 citation statements)

References 17 publications

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“…In their in vivo clastogenicity study, Hardman et al (32) reported that irinotecan significantly elevated MN frequency in mouse peripheral blood erythrocytes. Aydemir and Bilaloglu (33) found an increase in MN frequency in the bone marrow cells of mice treated with topotecan (an analogue of irinotecan). Kopjar et al (14) found a signifi cant increase in the MN frequency in human lymphocytes even at a lower dose of 4.6 µg mL -1 of irinotecan.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Cyto/Genotoxicity of Irinotecan in V79 Cells Using the Comet, Micronucleus, and Chromosome Aberration Assay

Kašuba

Rozgaj

Gamulin

et al. 2010

Archives of Industrial Hygiene and Toxicology

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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 µg mL -1 ), recommended monotherapy dose (9 µg mL -1 ), and recommended combined therapy dose (4.5 µg 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 signifi cance 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 signifi cant increase in micronucleated cells in respect to control, no dose-dependent relation was established among the treated cultures. Timedependent effect was also not observed. Kašuba V, et al. IRINOTECAN CYTO/GENOTOXICITY IN V79 CELLS Arh Hig Rada Toksikol 2010;61:1-9 KEY WORDS: alkaline comet assay, antineoplastic drug, cell cultures, DNA and cytogenetic damage, topoisomerase

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Section: Discussionmentioning

confidence: 99%

Assessment of Cyto/Genotoxicity of Irinotecan in V79 Cells Using the Comet, Micronucleus, and Chromosome Aberration Assay

Kašuba

Rozgaj

Gamulin

et al. 2010

Archives of Industrial Hygiene and Toxicology

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“…The cancer patients are treated either with single therapy or with combinations of more than one therapy depending on the type of cancer's advancement [1]. The therapeutic applications of antiproliferative drugs are restricted due to their toxic potentials, resistance, and genotoxicity [4]. The demand for relatively more effective and safer agents for the treatment of cancer is today's need.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antiproliferative Activity of Some Quinoline and Oxadiazole Derivatives

Ahsan¹,

Shastri²,

Yadav³

et al. 2016

Organic Chemistry International

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In continuance of our search for newer antiproliferative agents we report herein the synthesis and antiproliferative studies of two series (5a-j and 10a-c) of heterocyclic compounds. All the new compounds were characterized by IR, NMR, and mass spectral data. The antiproliferative activity of 10 compounds (5a-j) was carried out on HeLa (cervix cancer cell line) and MDA-MB-435 (melanoma) and LC 50 , TGI, and GI 50 were calculated, while the antiproliferative activity of 3 compounds (10a-c) was carried out against nine different panels of nearly 60 cell lines (NCI-60) according to the National Cancer Institute (NCI US) Protocol at 10 M. 1-(7-Hydroxy-4-methyl-2-oxoquinolin-1(2H)-yl)-3-(4-methoxylphenyl)urea (5j) was found to have antiproliferative activity with GI 50 of 35.1 M against HeLa (cervix cancer cell line) and 60.4 M against MDA-MB-435 (melanoma), respectively. The compounds 10a, 10b, and 10c showed antiproliferative activity with comparatively higher selectivity towards HOP-92 (Non-Small Cell Lung Cancer) with percent growth inhibitions (GIs) of 34.14, 35.29, and 31.59, respectively.

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“…But an in vivo clastogenicity study has shown that irinotecan significantly elevated the MN in the mouse peripheral blood erythrocytes [Hardman et al, 2002]. A marked increase in the total chromosomal aberrations and MN in the mouse bone marrow cells in mice treated with topotecan was observed [Aydemir and Bilaloglu, 2003]. In addition, in previous in vitro study carried out by Cunha et al [2002], topotecan was the most genotoxic and recombinogenic agent as compared with camptothecin or irinotecan in the Drosophila wing spot test.…”

Section: Introductionmentioning

confidence: 99%

Molecular cytogenetic evaluation of the mechanism of micronuclei formation induced by camptothecin, topotecan, and irinotecan

Attia

Aleisa

Bakheet

et al. 2009

Environ and Mol Mutagen

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We used the conventional bone marrow micronucleus test complemented with the fluorescent in situ hybridization with the minor satellite DNA probe to investigate the mechanisms of induction of micronuclei in mice treated with camptothecin and its clinical antineoplastic analogues topotecan and irinotecan. All experiments were performed with male Swiss albino mice. Single doses of 1 mg/kg camptothecin or 0.6 mg/kg topotecan were injected intraperitoneally and bone marrow was sampled at 30 hr (camptothecin) or 24 hr (topotecan) after treatment. A dose of 60 mg/kg irinotecan was injected intravenously, once every fourth day for 13 days and bone marrow was sampled 24 hr after the last treatment. In animals treated with camptothecin, a total of 1.07% micronuclei were found and 70% of them were centromere-negative, indicating their formation by DNA strand breaks and reflecting the predominant clastogenic activity of camptothecin. Exposure to topotecan and irinotecan yielded 1.71 and 0.83% micronuclei, respectively. About 52.7 and 48.8% of the induced micronuclei, respectively, were centromere-positive, indicating their formation by whole chromosomes and reflecting the aneugenic activity of both compounds. Correspondingly, about 47.3 and 51.2% of the induced micronuclei, respectively were centromere-negative, demonstrating that topotecan and irinotecan not only induce chromosome loss but also DNA strand breaks. Both the clastogenic and aneugenic potential of these drugs can lead to the development of secondary tumors and abnormal reproductive outcomes. Therefore, the clinical use of these agents must be weighed against the risks of secondary malignancies in cured patients and persistent genetic damage of their potential offspring.

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Genotoxicity of two anticancer drugs, gemcitabine and topotecan, in mouse bone marrow in vivo

Cited by 81 publications

References 17 publications

Assessment of Cyto/Genotoxicity of Irinotecan in V79 Cells Using the Comet, Micronucleus, and Chromosome Aberration Assay

Assessment of Cyto/Genotoxicity of Irinotecan in V79 Cells Using the Comet, Micronucleus, and Chromosome Aberration Assay

Synthesis and Antiproliferative Activity of Some Quinoline and Oxadiazole Derivatives

Molecular cytogenetic evaluation of the mechanism of micronuclei formation induced by camptothecin, topotecan, and irinotecan

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