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

IF 5.7 1区 农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY
Fourat Keskin, Hannah Noone, Mark J. Dickman, Esther Allen, William D. Mulcrone, Lars Holm Rasmussen, Hans Christian Bruun Hansen, Peter J. O’Connor, Andrew C. Povey, Geoffrey P. Margison, David M. Williams
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Abstract

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.

Abstract Image

蕨类致癌物Ptaquiloside在DNA中形成鸟嘌呤o6加合物
蕨类植物(蕨类植物)是一种生命力旺盛的植物,具有潜在的侵袭性,食用蕨类植物可引起农场动物的慢性疾病和癌症。蕨菜是一种可疑的人类致癌物,可能是由于摄入了被蕨菜污染的水、乳制品或食用了蕨菜类植物的牲畜的肉。一些社区的饮食中也食用蕨菜。Ptaquiloside (PTQ)是一种已知的蕨菜致癌物,是一种苯胺型糖苷,可形成高活性亲电试剂PTQ二烯酮,已知可在DNA中产生n7 -鸟嘌呤和n3 -腺嘌呤加合物。在这里,我们首次证明了PTQ二烯酮也在DNA中产生o6 -烷基鸟嘌呤(O6-PTBguanine)。由于DNA中的o6 -烷基鸟嘌呤具有致突变性,本研究提供了PTQ暴露与致癌性之间的潜在机制联系。o6 -甲基鸟嘌呤- dna甲基转移酶作用于其他o6 -烷基鸟嘌呤时,o6 -甲基鸟嘌呤修复不良,进一步突出了暴露于蕨菜和PTQ的潜在风险。
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来源期刊
Journal of Agricultural and Food Chemistry
Journal of Agricultural and Food Chemistry 农林科学-农业综合
CiteScore
9.90
自引率
8.20%
发文量
1375
审稿时长
2.3 months
期刊介绍: The Journal of Agricultural and Food Chemistry publishes high-quality, cutting edge original research representing complete studies and research advances dealing with the chemistry and biochemistry of agriculture and food. The Journal also encourages papers with chemistry and/or biochemistry as a major component combined with biological/sensory/nutritional/toxicological evaluation related to agriculture and/or food.
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