Black cohosh extract (BCE) is a widely used dietary supplement marketed to women to alleviate symptoms of gynecological ailments, yet its toxicity has not been well characterized. The National Toxicology Program (NTP) previously reported significant increases in micronucleated erythrocytes in peripheral blood of female Wistar Han rats and B6C3F1/N mice administered 15-1,000 mg BCE/kg/day by gavage for 90 days. These animals also developed a dose-dependent nonregenerative macrocytic anemia characterized by clinical changes consistent with megaloblastic anemia. Both micronuclei (MN) and megaloblastic anemia can arise from disruption of the folate metabolism pathway. The NTP used in vitro approaches to investigate whether the NTP's test lot of BCE, BCEs from various suppliers, and root powders from BC and other cohosh species, were genotoxic in general, and to gain insight into the mechanism of action of BCE genotoxicity. Samples were tested in human TK6 lymphoblastoid cells using the In Vitro MicroFlow® MN assay. The NTP BCE and a BC extract reference material (XRM) were tested in the MultiFlow® DNA Damage assay, which assesses biomarkers of DNA damage, cell division, and cytotoxicity. The NTP BCE and several additional BCEs were tested in bacterial mutagenicity assays. All samples induced MN when cells were grown in physiological levels of folic acid. The NTP BCE and BC XRM produced activity patterns consistent with an aneugenic mode of action. The NTP BCE and five additional BCEs were negative in bacterial mutagenicity tests. These findings show that black cohosh preparations induce chromosomal damage and may pose a safety concern. Environ. Mol. Mutagen. 59:416-426, 2018. © 2018 Published 2018. This article is a US Government work and is in the public domain in the USA.

中文翻译：

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黑升麻提取物和粉末在人体细胞中诱导微核，这是遗传损伤的生物标记。

黑升麻提取物（BCE）是一种广泛销售给女性的膳食补充剂，可减轻妇科疾病的症状，但其毒性尚未得到很好的表征。美国国家毒理学计划（NTP）先前曾报道雌性Wistar Han大鼠和B6C3F1 / N小鼠经管饲法给予15-1,000 mg BCE / kg /天，持续90天，其外周血中的微核红细胞显着增加。这些动物还发展出剂量依赖性的非再生性大细胞性贫血，其特征是与巨幼细胞性贫血相一致的临床变化。叶酸代谢途径的破坏可引起微核（MN）和巨幼细胞性贫血。NTP使用了体外方法来调查NTP的BCE测试批次，来自不同供应商的BCE以及来自BC和其他升麻物种的根粉，通常具有遗传毒性，并且可以深入了解BCE遗传毒性的作用机理。使用MN法体外在人TK6淋巴母细胞中测试样品。NTP BCE和BC提取物参考材料（XRM）在MultiFlow®DNA损伤测定中进行了测试，该测定可评估DNA损伤，细胞分裂和细胞毒性的生物标志物。在细菌诱变分析中测试了NTP BCE和其他几个BCE。当细胞以生理水平的叶酸生长时，所有样品均诱导MN。NTP BCE和BC XRM产生的活性模式与中性作用模式一致。NTP BCE和另外五个BCE在细菌诱变性测试中均为阴性。这些发现表明，黑色升麻制剂会引起染色体损伤，并可能引起安全隐患。环境。大声笑 诱变剂。59：416-426，