Formation of DNA adducts and mechanism of mutagenesis induced by nanomaterials

纳米材料由于其特性而有用，并且通常用于各个领域。纳米级磁铁矿在医药和工业领域有着广泛的应用，但其毒理学性质尚未得到很好的研究。在我们之前的研究中，我们发现，通过对ICR小鼠肺进行彗星试验分析，以0.05或0.2 mg/只动物的剂量单次注入MGT，其DNA损伤约为溶剂注入ICR小鼠的2 - 3倍。在这项研究中，一项全面的DNA加合物分析（DNA加合物组）显示，产生了一系列广泛的DNA加合物，包括乙烯基-dA和庚酮-乙烯基-dC，并且大多数被确定为MGT暴露组中主要贡献者的DNA加合物可能来自炎症。这些结果表明，炎症反应可能参与了MGT在小鼠肺中诱导的遗传毒性。

Nanomaterials are useful owing to their characteristic properties and are commonly used in various fields. Nanosized magnetite (MGT) is widely utilized in medicinal and industrial fields; however, their toxicological properties are not well studied. In our previous study, we found that DNA damage analyzed by the comet assay of the lungs of ICR mice intratracheally instilled with a single dose of MGT at 0.05 or 0.2 mg/animal was approximately two- to three-fold greater than that of vehicle-instilled ICR mice. In this study, a comprehensive DNA adduct analysis (DNA adductome) revealed that a broad array of DNA adducts, including etheno-dA and heptanone-etheno-dC, were produced and that most of the DNA adducts determined as the major contributors in the MGT-exposed group could be derived from inflammation. These findings suggest that inflammatory responses are probably involved in the genotoxicity induced by MGT in the lungs of mice.