title: Estragole: a weak direct-acting food-borne genotoxin and potential carcinogen.
abstract: We evaluated the genotoxicity of the food-flavouring agent estragole in V79 cells using the sister chromatid exchange (SCE) assay and the alkaline comet assay. Unexpectedly, we observed an increase in SCE without an exogenous biotransformation system (S9) and a decrease in its presence. Positive results were also observed in the alkaline comet assay without S9, indicating DNA strand breakage. To ascertain repair of damage, we performed the comet assay in V79 cells after two hours of recovery, and observed a reduction of the genotoxic response. Estragole did not produce strand breaks in plasmid DNA in vitro. We then evaluated the formation of DNA adducts in V79 cells by use of the (32)P-postlabelling assay and detected a dose-dependent formation of DNA adducts, which may be responsible for its genotoxicity. We then assayed estragole in the comet assay with two CHO cell lines, a parental AA8 cell line, and an XRCC1-deficient cell line, EM9. Results confirmed the genotoxicity of estragole without biotransformation in both cell lines, although the genotoxicity in EM9 cells compared with that in AA8 cells was not significantly different, suggesting that the XRCC1 protein is not involved in the repair of estragole-induced lesions. Estragole induces apoptosis, but only with high doses (2000μM), and after long treatment periods (24h). Overall, our results suggest that estragole, besides being metabolized to genotoxic metabolites, is a weak direct-acting genotoxin that forms DNA adducts.
authors.affiliation: CIGMH, Department of Genetics, Faculty of Medical Sciences, Universidade Nova de Lisboa, R. da Junqueira 100, P 1349-008 Lisboa, Portugal.
authors.forename: Célia
authors.initials: C
authors.lastname: Martins
authors.affiliation: CIGMH, Department of Genetics, Faculty of Medical Sciences, Universidade Nova de Lisboa, R. da Junqueira 100, P 1349-008 Lisboa, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Cação
authors.affiliation: Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton SM2 5NG, UK.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Cole
authors.affiliation: Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton SM2 5NG, UK.
authors.forename: David H
authors.initials: DH
authors.lastname: Phillips
authors.affiliation: CIGMH, Department of Genetics, Faculty of Medical Sciences, Universidade Nova de Lisboa, R. da Junqueira 100, P 1349-008 Lisboa, Portugal; Department of Life Sciences, Faculty of Sciences and Technology, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Laires
authors.affiliation: CIGMH, Department of Genetics, Faculty of Medical Sciences, Universidade Nova de Lisboa, R. da Junqueira 100, P 1349-008 Lisboa, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Rueff
authors.affiliation: CIGMH, Department of Genetics, Faculty of Medical Sciences, Universidade Nova de Lisboa, R. da Junqueira 100, P 1349-008 Lisboa, Portugal. Electronic address: sebastiao.rodrigues@fcm.unl.pt.
authors.forename: António S
authors.initials: AS
authors.lastname: Rodrigues
mesh_terms: D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000633:toxicity*; D017209:Apoptosis; D016466:CHO Cells; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D020552:Comet Assay; D006224:Cricetinae; D003412:Cricetulus; D018736:DNA Adducts; D004249:DNA Damage; D004260:DNA Repair; D005421:Flavoring Agents / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D012854:Sister Chromatid Exchange
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; D002273:Carcinogens; D018736:DNA Adducts; D005421:Flavoring Agents; D009153:Mutagens; C007633:estragole