Fontana Caroline, Kirsch Anaïs, Seidel Carole, Marpeaux Léa, Darne Christian, Gaté Laurent, Remy Aurélie, Guichard Yves
Institut National de Recherche et de Sécurité, Département de Toxicologie et de Biométrologie, 1 rue du Morvan, CS 60027, 54519 Vandœuvre Cedex, France.
Institut National de Recherche et de Sécurité, Département de Toxicologie et de Biométrologie, 1 rue du Morvan, CS 60027, 54519 Vandœuvre Cedex, France.
Mutat Res Genet Toxicol Environ Mutagen. 2017 Nov;823:22-27. doi: 10.1016/j.mrgentox.2017.08.002. Epub 2017 Aug 24.
Synthetic amorphous silica nanoparticles (SAS) are among the most widely produced and used nanomaterials, but little is known about their carcinogenic potential. This study aims to evaluate the ability of four different SAS, two precipitated, NM-200 and NM-201, and two pyrogenic, NM-202 and NM-203, to induce the transformation process. For this, we used the recently developed in vitro Bhas 42 cell transformation assay (CTA). The genome of the transgenic Bhas 42 cells contains several copies of the v-Ha-ras gene, making them particularly sensitive to tumor-promoter agents. The Bhas 42 CTA, which includes an initiation assay and a promotion assay, was validated in our laboratory using known soluble carcinogenic substances. Its suitability for particle-type substances was verified by using quartz Min-U-Sil 5 (Min-U-Sil) and diatomaceous earth (DE) microparticles. As expected given their known transforming properties, Min-U-Sil responded positively in the Bhas 42 CTA and DE responded negatively. Transformation assays were performed with SAS at concentrations ranging from 2μg/cm to 80μg/cm. Results showed that all SAS have the capacity to induce transformed foci, interestingly only in the promotion assay, suggesting a mode of action similar to tumor-promoter substances. NM-203 exhibited transforming activity at a lower concentration than the other SAS. In conclusion, this study showed for the first time the transforming potential of different SAS, which act as tumor-promoter substances in the Bhas 42 model of cell transformation.
合成无定形二氧化硅纳米颗粒（SAS）是生产和使用最为广泛的纳米材料之一，但人们对其致癌潜力却知之甚少。本研究旨在评估四种不同的SAS（两种沉淀法制备的NM - 200和NM - 201，以及两种热解法制备的NM - 202和NM - 203）诱导转化过程的能力。为此，我们使用了最近开发的体外Bhas 42细胞转化试验（CTA）。转基因Bhas 42细胞的基因组包含多个v - Ha - ras基因拷贝，使其对肿瘤促进剂特别敏感。包括启动试验和促进试验的Bhas 42 CTA在我们实验室中使用已知的可溶性致癌物质进行了验证。通过使用石英Min - U - Sil 5（Min - U - Sil）和硅藻土（DE）微粒验证了其对颗粒型物质的适用性。鉴于其已知的转化特性，正如预期的那样，Min - U - Sil在Bhas 42 CTA中呈阳性反应，而DE呈阴性反应。使用浓度范围为2μg/cm至80μg/cm的SAS进行转化试验。结果表明，所有SAS都有诱导转化灶的能力，有趣的是，仅在促进试验中如此，这表明其作用模式类似于肿瘤促进剂物质。NM - 203在比其他SAS更低的浓度下表现出转化活性。总之，本研究首次表明了不同SAS的转化潜力，它们在Bhas 42细胞转化模型中作为肿瘤促进剂物质发挥作用。
