Genotoxicity of doxorubicin in F344 rats by combining the comet assay, flow-cytometric peripheral blood micronucleus test, and pathway-focused gene expression profiling
Version of Record online: 24 OCT 2013
Copyright © 2013 Wiley Periodicals, Inc.
Environmental and Molecular Mutagenesis
Volume 55, Issue 1, pages 24–34, January 2014
How to Cite
Manjanatha, M. G., Bishop, M. E., Pearce, M. G., Kulkarni, R., Lyn-Cook, L. E. and Ding, W. (2014), Genotoxicity of doxorubicin in F344 rats by combining the comet assay, flow-cytometric peripheral blood micronucleus test, and pathway-focused gene expression profiling. Environ. Mol. Mutagen., 55: 24–34. doi: 10.1002/em.21822
- Issue online: 23 DEC 2013
- Version of Record online: 24 OCT 2013
- Manuscript Revised: 18 SEP 2013
- Manuscript Accepted: 18 SEP 2013
- Manuscript Received: 25 JUL 2013
- 1999. Single cell gel electrophoresis: detection of DNA damage at different levels of sensitivity. Electrophoresis 20:2133–2138. , , .
- 2009. DNA oxidation: Investigating its key role in environmental mutagenesis with the comet assay. Mutat Res 674:101–108. , , .
- 2004. Parallel evaluation of doxorubicin-induced genetic damage in human lymphocytes and sperm using the comet assay and spectral karyotyping. Mutagenesis 19:313–318. , , , .
- 2007. Adriamycin-induced oxidative mitochondrial cardiotoxicity. Cell Biol Toxicol 23:15–25. , .
- 1977. Doxorubicin hydrochloride-associated renal failure. Arch Intern Med 137:385–389. , , , .
- 2003. Macrophage migration inhibitory factor: A regulator of innate immunity. Nat Rev Immunol 3:791–800. , .
- 2007. Molecualar and cellular mechanisms of anthracyclin cardiotoxicity. Cardiovasc Toxicol 7:114–121. , , , , .
- 2004. The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol 26:249–261. .
- 1990. Induction of stable transcriptional blockage sites by Adriamycin: GpC specificity of apparent adriamycin-DNA adducts and dependence on iron (III) ions. Biochemistry 29:5638–5646. , .
- 1994. Formation of adriamycin-DNA adducts in vitro. Nucleic Acids Res 22:2296–2303. , , , .
- 1989. Effects of ICRF-187 on the cardiac and renal toxicity of epirubicin in spontaneously hypertensive rats. Cancer Chemother Pharmacol 23:269–275. , , .
- 2006. Influence of low-molecular weight heparin derivative on the nitric oxide levels and apoptotic DNA damage in adriamycin-induced cardiac and renal toxicity. Toxicology 217:176–183. , .
- 2011. Methyleugenol genotoxicity in the Fischer 344 rat using the comet assay and pathway-focused gene expression profiling. Toxicol Sci 123:103–112. , , , , , , , .
- 1980. Enzymatic defenses of the mouse heart against reactive oxygen metabolites: Alterations produced by doxorubicin. J Clin Invest 65:128–135. , , .
- 2000. THE COMET ASSAY, modified for detection of oxidized bases with the use of bacterial repair endonucleases. http://www.cometassayindia.org/Dusinska-protocol.PDF. .
- 2002. Childhood cancer survival in Europe and the United States. Cancer 95:1767–1772. , , , , .
- 1999. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol 57:727–741. .
- 2008. Anthracycline cardiotoxicity: From bench to bedside. J Clin Oncol 26:3777–3784. , , , , , .
- 1985. Doxorubicin–induced congestive heart failure in adults. Cancer 56:1361–1365. , , , , , , .
- 2007. DNA damage measured by comet assay and 8-OH-dG formation related to blood chemical analyses in aged rats. J Toxicol Sci 32:249–259. , , , .
- 1998. Animal models of anthracycline cardiotoxicity: Basic mechanisms and cardioprotective activity. Prog Pediatr Cardiol 8:49–58. , .
- 1988. Protective effect of ICRF-187 on doxorubicin-induced cardiac and renal toxicity in spontaneously hypertensive (SHR) and normotensive (WKY) rats. Toxicol Appl Pharmacol 92:42–53. , , .
- JaCVAM. 2009. International validation of the in vivo alakaline comet assay for the detection of genotoxic carcinogens. Version 14.2. http://Cometassay.com/JaCVAM.PDF.
- 2006. Cancer statistics. CA Cancer J Clin 56:106–130. , , , , , , .
- 1986. Comparison of adriamycin uptake n chick embryo heart and liver cells of murine L5178Y lymphoblasts in vitro: role of drug uptake in cardiotoxicity. Cancer Res 46:218–223. , , .
- 1997. Clinical cardiotoxicity following anthracycline treatment for childhood cancer: The pediatric Oncology Group Experience. J Clin Oncol 15:1544–1552. , , , , , .
- 1983. Meiotic micronuclei induced by adriamycin in male rats. Mutat Res 119:79–82. .
- 2006. DNA damage is an early event in doxorubicin-inducedcardiac myocyte death. Am J Physiol Heart Cir Physiol 291:H1273–H1280. , , , , , , .
- 2006. The relevance of information generated by in vitro experimental models to clinical doxorubicin cardiotoxicity. Leuk Lymphoma 47:1454–1458. , , .
- 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408. , and .
- 2006. Genotoxicity of acrylamide and its metabolite glycidamide administered in drinking water to male and female Big Blue mice. Environ Mol Mutagen 47:6–17. , , , , , , .
- 2012. Exercise preconditioning modulates genotoxicity induced by doxorubicin in multiple organs of rats. Cell Biochem Funct 30:293–296. , , , , , .
- 2008. Cardiotoxicity of antitumor drugs. Chem Res Toxicol 21:978–989. , , .
- 1977. Adriamycin-induced cardiotoxicity (cardiomyopathy and congestive heart failure) in rats. Cancer Res 37:2705–2713. , , .
- 1998. The role of iron in doxorubicin-induced cardiomyopathy. Semin Oncol 25:10–14. .
- 2008. An in vivo comet assay of multiple organs (liver, kidney and bone marrow) in mice treated with methyl methanesulfonate and acetaminophen accompanied by hematology and/or blood chemistry. J Toxicol Sci 33:515–524. , , , .
- 1989. DNA sequence specific adducts of adriamycin and mitomycin C. FEBS Lett 246:233–240. , , .
- 1997. In vivo genotoxicity of heterocyclic amines detected by a modified alkaline single cell gel electrophoresis assay in a multiple organ study in the mouse. Mutat Res 395:57–73. , , , , , , , .
- 2000. The comet assay with multiple mouse organs: comparison of comet assay results and carcinogenicity with 208 chemicals selected from the IARC monographs and U.S. NTP Carcinogenicity Database. Crit Rev Toxicol 30:629–799. , , , , , , .
- 2009. Anthracycline-induced cardiotoxicity: Overview of studies examining the roles of oxidative stress and free cellular iron. Pharmacol Rep 61:154–171. , , , , , .
- 1987. Subcellular effects of adriamycin in the heart: A concize review. J Mol Cell Cardiol 19:817–828. , , .
- 1988. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191. , , , .
- 2006. hOGG1 recognizes oxidative damage using the comet assay with greater specificity than FPG or ENDOIII. Mutagenesis 21:185–190. , , .
- 2007. Doxorubicin induced cardiomyopathy from the cardiotoxic mechanisms to management. Prog Cardiovasc Dis 49:330–352. , .
- 2000. Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35:206–221. , , , , , , , , , .
- 2010. Oral glutamine protects against acute doxorubicin-induced cardiotoxicity of tumor-bearing rats. J Nutr 140:44–48. , , , .
- 2006. New insights into doxorubicin-induced cardiotoxicity: the critical role of cellular energetics. J Mol Cell Cardiol 41:389–405. , , , , .
- 2009. Multivariate analysis of variance test for gene set analysis. Bioinformatics 25:897–903. , .
- 1996. Doxorubicin-induced apoptosis in spontaneously hypertensive rats: differential effects in heart, kidney, and intestine and inhibition by ICRF-187. J Mol Cell Cardiol 28:1931–1943. , , , .
- 2001. Cumulative and irreversible cardiac mitochondrial dysfunction induced by doxorubicin. Cancer Res 61:771–777. , , , , .