Protection of halogenated DNA from strand breakage and sister-chromatid exchange induced by the topoisomerase I inhibitor camptothecin

Orta, Manuel Luís; Mateos, Santiago; Cantero, Gloria; Wolff, Lisa J.; Cortés, Felipe

doi:10.1016/j.mrfmmm.2007.06.012

Cited by 7 publications

(2 citation statements)

References 49 publications

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“…En un primer ciclo de incorporación del BrdU, se logrará la sustitución de la timidina en las cromátidas hermanas, en el siguiente ciclo de duplicación, se tendrá una cromátida monosustituida (de coloración oscura) mientras que la otra será bisustituida (de coloración pálida), lográndo una diferenciación química de las dos cromátidas. La coloración diferencial permite visualizar los intercambios ocurridos entre las cromátidas hermanas (15).…”

Section: Eficiencia De Clonación En Células Chounclassified

Evaluación biológica de una fracción de la esponja marina Topsentia ophiraphidites del Caribe colombiano

et al. 2013

Rev MVZ Córdoba

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RESUMENObjetivo. Evaluar la actividad antiproliferativa y genotóxica de una fracción con actividad citotóxica obtenida de la esponja marina del Caribe colombiano Topsentia ophiraphidites (Fracción T4). Materiales y métodos. La fracción T4 de la esponja marina Topsentia ophiraphidites fue obtenida en el laboratorio de Productos Naturales Marinos de la Universidad de Antioquia. La actividad antiproliferativa se evaluó mediante ensayos de eficiencia de clonación, función de acumulación y cinética proliferativa por intercambio de cromátidas hermanas (ICH); la actividad genotóxica se evaluó mediante electroforesis en gel de células individuales (Ensayo cometa) e intercambio de cromátidas hermanas (ICH). Todas las pruebas fueron realizadas sobre las líneas celulares Jurkat y CHO. Resultados. La fracción T4 afectó el ciclo celular de las células CHO y mostró daño genotóxica crónico en las células Jurkat. Conclusiones. Se recomienda la evaluación de la fracción T4 en otras líneas celulares derivadas de tumor con el fin de determinar un posible efecto diferencial, además de evaluar otras actividades de tipo antimicrobiano, antimalárico, entre otros.

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Section: Eficiencia De Clonación En Células Chounclassified

Evaluación biológica de una fracción de la esponja marina Topsentia ophiraphidites del Caribe colombiano

et al. 2013

Rev MVZ Córdoba

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“…The antitumor activity of camptothecin is thought to be due to its ability to stabilize the reversible covalent DNAtopoisomerase I complex [Hsiang et al, 1985;Giovanella et al, 1989;Liu et al, 2000;Li et al, 2006;Pommier, 2006;Hartmann and Lipp 2006], preventing the religation step of the breakage/rejoining reaction mediated by the enzyme. The net result is that the drug causes fragmentation of chromosomal DNA, cell death and extensive sister chromatid exchange and chromosomal aberrations [Hsiang et al, 1989;Backer et al, 1990;Holmström and Winters, 1992;Mosesso et al, 2000;Sortibrán et al, 2006;Orta et al, 2008]. Elucidation of the specific target and mechanisms of camptothecin has stimulated intensive efforts to identify novel analogues that overcome the drawbacks of the natural camptothecin molecule, which include low solubility in water; severe and unpredictable toxicity, including hemorrhagic cystitis; reversibility of the drug-target interaction; lactone instability; and drug resistance [Porter and Champoux, 1989;De Cesare et al, 2001;Zunino and Pratesi, 2004].…”

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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Oxidative stress and endoreduplication induced by blue light exposure to CHO cells

Wall

Gius

Buglewicz

et al. 2019

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Protection of halogenated DNA from strand breakage and sister-chromatid exchange induced by the topoisomerase I inhibitor camptothecin

Cited by 7 publications

References 49 publications

Evaluación biológica de una fracción de la esponja marina Topsentia ophiraphidites del Caribe colombiano

Evaluación biológica de una fracción de la esponja marina Topsentia ophiraphidites del Caribe colombiano

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

Oxidative stress and endoreduplication induced by blue light exposure to CHO cells

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