Genotoxicity of the alkenylbenzenes alpha- and beta-asarone, myristicin and elimicin as determined by the UDS assay in cultured rat hepatocytes
- PMID: 8157216
- DOI: 10.1016/0278-6915(94)90194-5
Genotoxicity of the alkenylbenzenes alpha- and beta-asarone, myristicin and elimicin as determined by the UDS assay in cultured rat hepatocytes
Abstract
While the alkenylbenzenes alpha- and beta-asarone are hepatocarcinogenic in rodents, myristicin and elimicin, two other alkenylbenzenes, are not. The present study investigated the mechanism of genotoxicity of the asarones to elucidate the role of cytochrome P-450 and obtain further information about the relationships between the structure, metabolism and genotoxicity of the alkenylbenzenes. The data on the ability of these compounds to induce unscheduled DNA synthesis (UDS) in hepatocytes derived from male Fischer 344 rats are presented in this paper. Cytotoxicity was assessed by lactate dehydrogenase leakage. Elimicin and alpha- and beta-asarone are genotoxic in the UDS assay but myristicin is not. The genotoxicity of the asarones is inhibited by the cytochrome P-450 inhibitor cimetidine but the sulfotransferase inhibitor pentachlorophenol (PCP) is without effect. The major metabolite of the asarones in hepatocytes was identified by liquid chromatography-mass spectrometry as 2,4,5-trimethoxycinnamic acid but this was not genotoxic when tested separately. Simple allylbenzenes such as safrole, estragole and methyleugenol are activated by sequential 1-hydroxylation and sulfation, and this is the likely mechanism of the genotoxicity of elimicin. The propenyl analogues isosafrole, anethole and methylisoeugenol, which cannot undergo 1-hydroxylation, are not genotoxic. The positive results obtained with the asarones suggest the occurrence of a novel activation 'option' for alkenylbenzenes which features a 2-methoxy group in the aromatic ring.
Similar articles
-
Myristicin and Elemicin: Potentially Toxic Alkenylbenzenes in Food.Foods. 2022 Jul 5;11(13):1988. doi: 10.3390/foods11131988. Foods. 2022. PMID: 35804802 Free PMC article. Review.
-
Structure-genotoxicity relationships of allylbenzenes and propenylbenzenes: a quantum chemical study.Chem Res Toxicol. 1994 Jan-Feb;7(1):73-6. doi: 10.1021/tx00037a011. Chem Res Toxicol. 1994. PMID: 8155828
-
Structure-specificity of the genotoxicity of some naturally occurring alkenylbenzenes determined by the unscheduled DNA synthesis assay in rat hepatocytes.Food Chem Toxicol. 1990 Aug;28(8):537-42. doi: 10.1016/0278-6915(90)90152-d. Food Chem Toxicol. 1990. PMID: 2242826
-
Comparative induction of unscheduled DNA synthesis in cultured rat hepatocytes by allylbenzenes and their 1'-hydroxy metabolites.Food Chem Toxicol. 1992 Oct;30(10):831-6. doi: 10.1016/0278-6915(92)90047-o. Food Chem Toxicol. 1992. PMID: 1427504
-
Toxicological evaluation of myristicin.Nat Toxins. 1997;5(5):186-92. doi: 10.1002/nt.3. Nat Toxins. 1997. PMID: 9496377 Review.
Cited by
-
Food-Borne Chemical Carcinogens and the Evidence for Human Cancer Risk.Foods. 2022 Sep 13;11(18):2828. doi: 10.3390/foods11182828. Foods. 2022. PMID: 36140952 Free PMC article. Review.
-
Essential Oils as Multicomponent Mixtures and Their Potential for Human Health and Well-Being.Front Pharmacol. 2022 Aug 24;13:956541. doi: 10.3389/fphar.2022.956541. eCollection 2022. Front Pharmacol. 2022. PMID: 36091825 Free PMC article. Review.
-
Myristicin and Elemicin: Potentially Toxic Alkenylbenzenes in Food.Foods. 2022 Jul 5;11(13):1988. doi: 10.3390/foods11131988. Foods. 2022. PMID: 35804802 Free PMC article. Review.
-
Phase II Metabolism of Asarone Isomers In Vitro and in Humans Using HPLC-MS/MS and HPLC-qToF/MS.Foods. 2021 Aug 29;10(9):2032. doi: 10.3390/foods10092032. Foods. 2021. PMID: 34574142 Free PMC article.
-
Mode of action-based risk assessment of genotoxic carcinogens.Arch Toxicol. 2020 Jun;94(6):1787-1877. doi: 10.1007/s00204-020-02733-2. Epub 2020 Jun 15. Arch Toxicol. 2020. PMID: 32542409 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources