Incorporation of silver nanoparticles (AgNPs) in toothpaste, food containers, dietary supplements and other consumer products can result in oral exposure to AgNPs and/or silver ions (Ag+) released from the surface of AgNPs. To examine whether ingestion of AgNPs or Ag+ results in genotoxic damage and whether AgNP coatings modulate the effect, we exposed mice orally to 20 nm citrate-coated AgNPs, polyvinylpyrrolidone (PVP)-coated AgNPs, silver acetate or respective vehicles at a 4 mg/kg dose (equivalent to 800x the EPA reference dose for Ag) for 7 days. Genotoxicity was examined in the systemic circulation and bone marrow at 1, 7, and 14 days post-exposure. We found that citrate-coated AgNPs induced chromosomal damage in bone marrow and oxidative DNA damage and double strand breaks in peripheral blood. These damages persisted for at least 14 days after exposure termination. Because oxidative DNA damage and strand breaks are repaired rapidly, their presence after exposure cessation indicates that citrate-coated AgNPs persist in the body. In contrast, PVP-coated AgNPs and silver acetate did not induce DNA or chromosomal damage at any time point measured. To determine whether coating-dependent genotoxicity is related to different AgNP changes in the gastrointestinal tract, we examined AgNP behavior and fate in an in vitro gastrointestinal digestion model using UV-visible spectroscopy and DLS. Citrate-coated AgNPs were more susceptible to agglomeration than PVP-coated AgNPs in digestive juices with or without proteins. In summary, AgNPs but not Ag+ are genotoxic following oral ingestion. Nanoparticle coatings modulate gastrointestinal transformation and genotoxicity of AgNPs, where higher agglomeration of AgNPs in gastrointestinal juices is associated with higher genotoxicity in tissues. Since genotoxicity is a strong indicator of cancer risk, further long-term studies focusing on cancer are warranted.

中文翻译：

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粒子涂层而非银离子介导小鼠模型中摄入的银纳米粒子的遗传毒性

在牙膏、食品容器、膳食补充剂和其他消费品中加入银纳米粒子 (AgNPs) 会导致口腔暴露于 AgNPs 和/或从 AgNPs 表面释放的银离子 (Ag+)。为了检查摄入 AgNPs 或 Ag+ 是否会导致基因毒性损伤以及 AgNP 涂层是否会调节这种作用，我们将小鼠口服暴露于 20 nm 柠檬酸盐涂层的 AgNPs、聚乙烯吡咯烷酮 (PVP) 涂层的 AgNPs、醋酸银或相应的载体，浓度为 4 mg/ kg 剂量（相当于 EPA 对 Ag 参考剂量的 800 倍），持续 7 天。在暴露后 1、7 和 14 天检查全身循环和骨髓中的基因毒性。我们发现柠檬酸盐包覆的 AgNPs 会诱导骨髓中的染色体损伤和外周血中的氧化性 DNA 损伤和双链断裂。这些损害在暴露终止后至少持续 14 天。由于氧化性 DNA 损伤和链断裂得到迅速修复，因此在停止暴露后它们的存在表明柠檬酸盐包覆的 AgNPs 在体内持续存在。相比之下，PVP 涂层的 AgNPs 和醋酸银在测量的任何时间点都不会引起 DNA 或染色体损伤。为了确定涂层依赖性基因毒性是否与胃肠道中不同的 AgNP 变化有关，我们使用紫外可见光谱和 DLS 在体外胃肠消化模型中检查了 AgNP 的行为和命运。在含或不含蛋白质的消化液中，柠檬酸盐包覆的 AgNPs 比 PVP 包覆的 AgNPs 更容易团聚。总之，AgNPs 但不是 Ag+ 在口服摄入后具有遗传毒性。纳米粒子涂层可调节 AgNPs 的胃肠转化和遗传毒性，其中 AgNPs 在胃肠液中的较高聚集与组织中较高的遗传毒性有关。由于基因毒性是癌症风险的重要指标，因此有必要对癌症进行进一步的长期研究。