title: Genotoxicity and endoreduplication inducing activity of the food flavouring eugenol.
abstract: 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 microM, demonstrating cytotoxicity at higher doses. S9 increased the induction of CAs in a dose-dependent manner to 15% at 2500 microM, 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 microM, 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 (0.1-0.5 microM), increasing the number of endoreduplicated cells from 0% (control) to 3.5% (0.5 microM). 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.
authors.affiliation: Department of Genetics, Faculty of Medical Sciences, Universidade Nova de Lisboa R. da Junqueira 96, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Maralhas
authors.forename: Ana
authors.initials: A
authors.lastname: Monteiro
authors.forename: Célia
authors.initials: C
authors.lastname: Martins
authors.forename: Michel
authors.initials: M
authors.lastname: Kranendonk
authors.forename: António
authors.initials: A
authors.lastname: Laires
authors.forename: José
authors.initials: J
authors.lastname: Rueff
authors.forename: António S
authors.initials: AS
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000139:chemically induced*; D006224:Cricetinae; D004249:DNA Damage / Q000187:drug effects*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D054659:Diketopiperazines; D004305:Dose-Response Relationship, Drug; D005054:Eugenol / Q000633:toxicity*; D005421:Flavoring Agents / Q000633:toxicity*; D009152:Mutagenicity Tests / Q000379:methods; D010879:Piperazines / Q000494:pharmacology
chemical_list: D054659:Diketopiperazines; D005421:Flavoring Agents; D010879:Piperazines; C070899:4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione; D005054:Eugenol; D004250:DNA Topoisomerases, Type II