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Methyleugenol genotoxicity in the Fischer 344 rat using the comet assay and pathway-focused gene expression profiling.
Toxicol Sci. 2011 Sep; 123(1):103-12.TS

Abstract

Methyleugenol (MEG), a constituent of human food, induces malignant tumors in multiple tissues of rats and mice. Although MEG forms DNA adducts and induces unscheduled DNA synthesis in rat liver, it is negative in many in vitro genetic toxicity assays. In the present study, we evaluated MEG-induced DNA damage in the rat using (1) the alkaline Comet assay, (2) the oxidative Comet assay, and (3) expression profiling of genes associated with DNA damage pathways. Male F344 rats received single oral doses of 400 or 1000 mg/kg body weight (bw) MEG and DNA damage was assessed by the Comet assay in liver, bladder, bone marrow, kidney, and lung 3 h and 24 h later. MEG failed to produce any increase in DNA damage. In addition, rats were given a single oral dose of 2000 mg/kg bw MEG, and Comet assays were performed with liver, bone marrow, and bladder 1, 3, 6, and 8 h later. With one exception (bone marrow at 8 h), no DNA damage was detected. Enzyme-modified Comet assays were conducted in parallel with standard Comet assays in liver. Whereas no MEG-induced DNA damage was detected following formamidopyrimidine DNA glycosylase digestion, digestion with endonuclease III resulted in increases in DNA damage at the 6- and 8-h sampling times. Gene expression analysis on the livers from MEG-exposed rats showed significant reduction in genes associated with DNA repair. The results indicate that MEG induces DNA damage in rat liver and that oxidative DNA damages may be partly responsible for the genotoxicity of MEG in rodents.

Authors+Show Affiliations

U.S. Food and Drug Administration, Jefferson Laboratories, National Center for Toxicological Research, Division of Genetic and Molecular Toxicology, Jefferson, Arkansas 72079, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

21659616

Citation

Ding, Wei, et al. "Methyleugenol Genotoxicity in the Fischer 344 Rat Using the Comet Assay and Pathway-focused Gene Expression Profiling." Toxicological Sciences : an Official Journal of the Society of Toxicology, vol. 123, no. 1, 2011, pp. 103-12.
Ding W, Levy DD, Bishop ME, et al. Methyleugenol genotoxicity in the Fischer 344 rat using the comet assay and pathway-focused gene expression profiling. Toxicol Sci. 2011;123(1):103-12.
Ding, W., Levy, D. D., Bishop, M. E., Lyn-Cook Lascelles, E., Kulkarni, R., Chang, C. W., Aidoo, A., & Manjanatha, M. G. (2011). Methyleugenol genotoxicity in the Fischer 344 rat using the comet assay and pathway-focused gene expression profiling. Toxicological Sciences : an Official Journal of the Society of Toxicology, 123(1), 103-12. https://doi.org/10.1093/toxsci/kfr153
Ding W, et al. Methyleugenol Genotoxicity in the Fischer 344 Rat Using the Comet Assay and Pathway-focused Gene Expression Profiling. Toxicol Sci. 2011;123(1):103-12. PubMed PMID: 21659616.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Methyleugenol genotoxicity in the Fischer 344 rat using the comet assay and pathway-focused gene expression profiling. AU - Ding,Wei, AU - Levy,Dan D, AU - Bishop,Michelle E, AU - Lyn-Cook Lascelles,E, AU - Kulkarni,Rohan, AU - Chang,Ching-We, AU - Aidoo,Anane, AU - Manjanatha,Mugimane G, Y1 - 2011/06/09/ PY - 2011/6/11/entrez PY - 2011/6/11/pubmed PY - 2011/12/21/medline SP - 103 EP - 12 JF - Toxicological sciences : an official journal of the Society of Toxicology JO - Toxicol Sci VL - 123 IS - 1 N2 - Methyleugenol (MEG), a constituent of human food, induces malignant tumors in multiple tissues of rats and mice. Although MEG forms DNA adducts and induces unscheduled DNA synthesis in rat liver, it is negative in many in vitro genetic toxicity assays. In the present study, we evaluated MEG-induced DNA damage in the rat using (1) the alkaline Comet assay, (2) the oxidative Comet assay, and (3) expression profiling of genes associated with DNA damage pathways. Male F344 rats received single oral doses of 400 or 1000 mg/kg body weight (bw) MEG and DNA damage was assessed by the Comet assay in liver, bladder, bone marrow, kidney, and lung 3 h and 24 h later. MEG failed to produce any increase in DNA damage. In addition, rats were given a single oral dose of 2000 mg/kg bw MEG, and Comet assays were performed with liver, bone marrow, and bladder 1, 3, 6, and 8 h later. With one exception (bone marrow at 8 h), no DNA damage was detected. Enzyme-modified Comet assays were conducted in parallel with standard Comet assays in liver. Whereas no MEG-induced DNA damage was detected following formamidopyrimidine DNA glycosylase digestion, digestion with endonuclease III resulted in increases in DNA damage at the 6- and 8-h sampling times. Gene expression analysis on the livers from MEG-exposed rats showed significant reduction in genes associated with DNA repair. The results indicate that MEG induces DNA damage in rat liver and that oxidative DNA damages may be partly responsible for the genotoxicity of MEG in rodents. SN - 1096-0929 UR - https://www.unboundmedicine.com/medline/citation/21659616/Methyleugenol_genotoxicity_in_the_Fischer_344_rat_using_the_comet_assay_and_pathway_focused_gene_expression_profiling_ L2 - https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kfr153 DB - PRIME DP - Unbound Medicine ER -