title: Multiple genotoxic activities of ptaquiloside in human lymphocytes: aneugenesis, clastogenesis and induction of sister chromatid exchange.
abstract: Ptaquiloside, a norsesquiterpene glycoside from bracken (Pteridium aquilinum), is a known carcinogen towards animals. Its genotoxicity is mainly attributed to its DNA-alkylating and clastogenic properties. This study analyses various modes of genotoxic action of ptaquiloside in human mononuclear blood cells. The alkaline comet assay was performed on cells exposed to 5μg/ml ptaquiloside for 5, 10, 20, 30, 40 or 50min. Tail length was used as a DNA-damage parameter. Assays to determine structural and numerical chromosomal aberrations and sister-chromatid exchange were conducted on cells exposed to 5, 10 or 20μg/ml ptaquiloside for 48h. The tail length showed maximum DNA damage at 20-30min, diminishing onwards. Highly significant (p<0.001) dose-dependent increases in structural and numerical chromosomal aberrations and SCE were observed in response to ptaquiloside. These results indicate that ptaquiloside is not only a DNA-alkylating agent, but expresses its genotoxicity through multiple mechanisms including clastogenesis, aneugenesis and the mechanism underlying SCE induction, which is not entirely understood. Recent studies support the role played by aneuploidy in oncogenesis, highlighting the importance of this endpoint for mutagenicity screening. SCE are thought to represent the long-term effects of mutagens and are an important genotoxicity biomarker. The present results also agree with data from epidemiological studies and from animal in vivo studies, further supporting the hypothesis that ptaquiloside may represent a significant threat to human health.
authors.affiliation: Abel Salazar Institute for Biomedical Sciences (ICBAS), University of Porto, Largo Prof. Abel Salazar 2, 4099-003 Porto, Portugal; LEPAE, Chemical Engineering Department, Engineering Faculty, University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: gildacosta@portugalmail.pt.
authors.forename: Rui M
authors.initials: RM
authors.lastname: Gil da Costa
authors.affiliation: Environmental Health Department, National Institute of Health, Rua Alexandre Herculano 321, 4000-055 Porto, Portugal. Electronic address: pcscoelho@gmail.com.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Coelho
authors.affiliation: Abel Salazar Institute for Biomedical Sciences (ICBAS), University of Porto, Largo Prof. Abel Salazar 2, 4099-003 Porto, Portugal. Electronic address: rasousa@icbas.up.pt.
authors.forename: Rosa
authors.initials: R
authors.lastname: Sousa
authors.affiliation: LEPAE, Chemical Engineering Department, Engineering Faculty, University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: mbastos@fe.up.pt.
authors.forename: Margarida M S M
authors.initials: MMSM
authors.lastname: Bastos
authors.affiliation: Abel Salazar Institute for Biomedical Sciences (ICBAS), University of Porto, Largo Prof. Abel Salazar 2, 4099-003 Porto, Portugal. Electronic address: bporto@icbas.up.pt.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Porto
authors.affiliation: Environmental Health Department, National Institute of Health, Rua Alexandre Herculano 321, 4000-055 Porto, Portugal. Electronic address: joao.teixeira@gmail.com.
authors.forename: João P
authors.initials: JP
authors.lastname: Teixeira
authors.affiliation: Abel Salazar Institute for Biomedical Sciences (ICBAS), University of Porto, Largo Prof. Abel Salazar 2, 4099-003 Porto, Portugal. Electronic address: malheiro@icbas.up.pt.
authors.forename: Isabel
authors.initials: I
authors.lastname: Malheiro
authors.affiliation: Abel Salazar Institute for Biomedical Sciences (ICBAS), University of Porto, Largo Prof. Abel Salazar 2, 4099-003 Porto, Portugal. Electronic address: calopes@icbas.up.pt.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity; D024422:Aneugens / Q000633:toxicity; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007189:Indans / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects*; D009153:Mutagens / Q000633:toxicity*; D012717:Sesquiterpenes / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000477:Alkylating Agents; D024422:Aneugens; D007189:Indans; D009153:Mutagens; D012717:Sesquiterpenes; C043680:ptaquiloside