Bracken Fern Carcinogen, Ptaquiloside, Forms a Guanine O6-Adduct in DNA.

Bracken fern (Pteridium sp.) is a viable and vigorous plant with invasive potential, ingestion of which causes chronic illness and cancers in farm animals. Bracken is a suspected human carcinogen, and exposure can result from ingestion of bracken-contaminated water, dairy products, or meat derived from livestock grazing on bracken fern. Bracken is also consumed in the diets of some communities. Ptaquiloside (PTQ), a known bracken carcinogen, is an illudane-type glycoside that forms a highly reactive electrophile, PTQ dienone, known to produce N7-guanine and N3-adenine adducts in DNA. Here, we demonstrate for the first time that PTQ dienone also produces an O6-alkylguanine (O6-PTBguanine) in DNA. Since O6-alkylguanines in DNA can be mutagenic, this work provides a potential mechanistic link between PTQ exposure and carcinogenicity. O6-PTBguanine is poorly repaired by O6-methylguanine-DNA methyltransferase that acts on other O6-alkylguanines, further highlighting the potential risk of exposure to bracken and PTQ.