Mutagenesis Advance Access originally published online on April 4, 2006
Mutagenesis 2006 21(3):199-204; doi:10.1093/mutage/gel017
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Genotoxicity and endoreduplication inducing activity of the food flavouring eugenol
1 Department of Genetics, Faculty of Medical Sciences, Universidade Nova de Lisboa R. da Junqueira 96, P 1349-008 Lisbon, Portugal 2 SABT, Faculty of Sciences and Technology, Universidade Nova de Lisboa Lisbon, Portugal
Eugenol (1-allyl-3-methoxy-4-hydroxybenzene; CAS No. 97-53-0), a compound extracted from clove oil and marjoram, is widely used as a food flavouring substance and is present in spices such as basil, cinnamon and nutmeg. It is also used in dentistry as an antiseptic and analgesic. Structural similarities with the class IIB IARC carcinogen safrole raises questions on its putative carcinogenicity. We evaluated the genotoxicity of eugenol in V79 cells using chromosomal aberrations (CAs), with and without rat liver biotransformation (S9). Eugenol induced CAs, with significant increases (3.5% aberrant cells) at 2500 µM, demonstrating cytotoxicity at higher doses. S9 increased the induction of CAs in a dose-dependent manner to 15% at 2500 µM, with a high frequency of chromatid exchanges. In particular, an increase of endoreduplicated cells was observed, from 0% at control levels to 2.3 and 5% at 2000 µM, without and with S9, respectively. Since endoreduplication has been linked to inhibition of topoisomerase II, the topoisomerase II inhibitor ICRF-193 was used as a control inducer of endoreduplication (0.10.5 µM), increasing the number of endoreduplicated cells from 0% (control) to 3.5% (0.5 µM). S9 did not influence endoreduplication by ICRF-193. Both eugenol and ICRF-193 were also assayed for inhibition of topoisomerase II, and both showed a dose-dependent inhibitory effect, with ICRF-193 being a more potent inhibitor. Our results confirm that eugenol is genotoxic and raises the possibility of it having topoisomerase II inhibiting activity.
*To whom correspondence should be addressed: Tel: +351 21 3610290; Fax: +351 21 3622018; E-mail: rueff.gene{at}fcm.unl.pt