The eucalyptus oil ingredient 1,8-cineol induces oxidative DNA damage

被引:37
作者
Doersam, Bastian [1 ]
Wu, Ching-Fen [2 ]
Efferth, Thomas [2 ]
Kaina, Bernd [1 ]
Fahrer, Joerg [1 ]
机构
[1] Univ Med Ctr Mainz, Dept Toxicol, D-55131 Mainz, Germany
[2] Johannes Gutenberg Univ Mainz, Inst Pharm & Biochem, Dept Pharmaceut Biol, D-55128 Mainz, Germany
关键词
1,8-Cineol; Eucalyptol; Eucalyptus oil; Genotoxicity; Oxidative DNA damage; DNA repair; DOUBLE-STRAND BREAKS; METHYL METHANESULFONATE; MAMMALIAN-CELLS; GENOTOXICITY; MONOTERPENES; EXPRESSION; REPELLENT; PROTECTS; REPAIR; AGENT;
D O I
10.1007/s00204-014-1281-z
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
The natural compound 1,8-cineol, also known as eucalyptol, is a major constituent of eucalyptus oil. This epoxy-monoterpene is used as flavor and fragrance in consumer goods as well as medical therapies. Due to its anti-inflammatory properties, 1,8-cineol is also applied to treat upper and lower airway diseases. Despite its widespread use, only little is known about the genotoxicity of 1,8-cineol in mammalian cells. This study investigates the genotoxicity and cytotoxicity of 1,8-cineol in human and hamster cells. First, we observed a significant and concentration-dependent increase in oxidative DNA damage in human colon cancer cells, as detected by the Formamidopyrimidine-DNA glycosylase (Fpg)-modified alkaline comet assay. Pre-treatment of cells with the antioxidant N-acetylcysteine prevented the formation of Fpg-sensitive sites after 1,8-cineol treatment, supporting the notion that 1,8-cineol induces oxidative DNA damage. In the dose range of DNA damage induction, 1,8-cineol did neither reduce the viability of colon cancer cells nor affected their cell cycle distribution, suggesting that cells tolerate 1,8-cineol-induced oxidative DNA damage by engaging DNA repair. To test this hypothesis, hamster cell lines with defects in BRCA2 and Rad51, which are essentials players of homologous recombination (HR)-mediated repair, were treated with 1,8-cineol. The monoterpene induced oxidative DNA damage and subsequent DNA double-strand breaks in the hamster cell lines tested. Intriguingly, we detected a significant concentration-dependent decrease in viability of the HR-defective cells, whereas the corresponding wild-type cell lines with functional HR were not affected. Based on these findings, we conclude that 1,8-cineol is weakly genotoxic, inducing primarily oxidative DNA damage, which is most likely tolerated in DNA repair proficient cells without resulting in cell cycle arrest and cell death. However, cells with deficiency in HR were compromised after 1,8-cineol treatment, suggesting a protective role of HR in response to high doses of 1,8-cineol.
引用
收藏
页码:797 / 805
页数:9
相关论文
共 34 条
[1]  
Andrade-Neto M, 1994, J ESSENT OIL RES, V6, P299
[2]   Inhaled 1,8-Cineole Reduces Inflammatory Parameters in Airways of Ovalbumin-Challenged Guinea Pigs [J].
Bastos, Vasco P. D. ;
Gomes, Antoniella S. ;
Lima, Francisco J. B. ;
Brito, Teresinha S. ;
Soares, Pedro M. G. ;
Pinho, Joao P. M. ;
Silva, Claudijane S. ;
Santos, Armenio A. ;
Souza, Marcellus H. L. P. ;
Magalhaes, Pedro J. C. .
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, 2011, 108 (01) :34-39
[3]   Artesunate Induces Oxidative DNA Damage, Sustained DNA Double-Strand Breaks, and the ATM/ATR Damage Response in Cancer Cells [J].
Berdelle, Nicole ;
Nikolova, Teodora ;
Quiros, Steve ;
Efferth, Thomas ;
Kaina, Bernd .
MOLECULAR CANCER THERAPEUTICS, 2011, 10 (12) :2224-2233
[4]   Mechanisms of human DNA repair: an update [J].
Christmann, M ;
Tomicic, MT ;
Roos, WP ;
Kaina, B .
TOXICOLOGY, 2003, 193 (1-2) :3-34
[5]   1,8-Cineol inhibits nuclear translocation of NF-κB p65 and NF-κB-dependent transcriptional activity [J].
Greiner, Johannes F. -W. ;
Mueller, Janine ;
Zeuner, Marie-Theres ;
Hauser, Stefan ;
Seidel, Thorsten ;
Klenke, Christin ;
Grunwald, Lena-Marie ;
Schomann, Timo ;
Widera, Darius ;
Sudhoff, Holger ;
Kaltschmidt, Barbara ;
Kaltschmidt, Christian .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2013, 1833 (12) :2866-2878
[6]   Oleuropein, a non-toxic olive iridoid, is an anti-tumor agent and cytoskeleton disruptor [J].
Hamdi, HK ;
Castellon, R .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 334 (03) :769-778
[7]   Anti-proliferative and apoptotic effects of oleuropein and hydroxytyrosol on human breast cancer MCF-7 cells [J].
Han, Junkyu ;
Talorete, Terence P. N. ;
Yamada, Parida ;
Isoda, Hiroko .
CYTOTECHNOLOGY, 2009, 59 (01) :45-53
[8]  
Harborne JB., 2001, Chemical dictionary of economic plants
[9]   Coping with stress: multiple ways to activate p53 [J].
Horn, H. F. ;
Vousden, K. H. .
ONCOGENE, 2007, 26 (09) :1306-1316
[10]  
Horvathova E, 2007, NEOPLASMA, V54, P478