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.