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.

Anticariogenic and cytotoxic activity of clove essential oil (Eugenia caryophyllata) against a large number of oral pathogens

“…The antibacterial activity of the essential oil may be associated with the high eugenol content, which has been tested previously and was found to have a significant antibiotic activity (Chaieb et al 2007;Zheng et al 1992). Eugenol is also used widely as an analgesic and antiseptic in clinical dentistry (Maralhas et al 2006). Its antibacterial activity against cariogenic bacteria including Streptococcus mutans and Streptococcus salivarius has been reported (Rasheed and Haider 1998).…”

Safety assessment of potential food ingredients in canine hepatocytes

“…We do not know whether these unidentified constituents contributed to some of the toxicity observed. The amount of individual chemicals comprising each batch should be listed since methyleugenol has been reported to be genotoxic (Maralhas et al, 2006).…”

“…Its main ingredient EUG functions as an antioxidant (Ogata et al, 2000) and is widely used in the food industry and dentistry as a cement and sedative agent (Markowitz et al, 1992). It has been shown to induce chromosomal aberrations and endoreduplication in vitro (Maralhas et al, 2006). Other research suggests that methyleugenol may cause DNA damage in rat liver (Ding et al, 2011).…”

Beneficial Health Effects of Bioactive Compounds Present in Spices and Aromatic Herbs

“…Increased expression of COX-2 gene induced by TA was also abolished by eugenol. Maralhas et al [31] showed that eugenol induces chromosomal aberrations and endo-reduplication in V79 cells, in the absence of an exogenous biotransformation system, suggesting a direct acting genotoxic mechanism, possibly as a topoisomerase II inhibitor. Abraham [32] indicated that eugenol pre-treatment can lead to a moderate reduction in genotoxicity of cyclophosphamide, procarbazine, N-methyl-N'-nitro-N-nitrosoguanidine and urethane.…”