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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.
AuthorsRui M Gil da Costa, Patrícia Coelho, Rosa Sousa, Margarida M S M Bastos, Beatriz Porto, João P Teixeira, Isabel Malheiro, Carlos Lopes
JournalMutation research (Mutat Res) Vol. 747 Issue 1 Pg. 77-81 (Aug 30 2012) ISSN: 0027-5107 [Print] Netherlands
PMID22565221 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Alkylating Agents
  • Aneugens
  • Indans
  • Mutagens
  • Sesquiterpenes
  • ptaquiloside
Topics
  • Alkylating Agents (toxicity)
  • Aneugens (toxicity)
  • Comet Assay
  • DNA Damage (drug effects)
  • Dose-Response Relationship, Drug
  • Humans
  • Indans (toxicity)
  • Lymphocytes (drug effects)
  • Mutagens (toxicity)
  • Sesquiterpenes (toxicity)
  • Sister Chromatid Exchange (drug effects)
  • Time Factors

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