Laboratorio de Carcinogénesis y Toxicología, Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Av. de los Barrios No. 1, Los Reyes Iztacala, Tlalnepantla de Baz CP 54090, Estado de México, Mexico.
Atmospheric Organic Aerosol Chemical Speciation Group, Instituto de Ciencias de la Atmósfera y Cambio Climático, Universidad Nacional Autónoma de México, AP 70228, Ciudad de México 04510, Mexico.
Toxicology. 2022 Aug;478:153280. doi: 10.1016/j.tox.2022.153280. Epub 2022 Aug 13.
Titanium dioxide food grade (E171) is one of the most used food additives containing nanoparticles. Recently, the European Food Safety Authority indicated that E171 could no longer be considered safe as a food additive due to the possibility of it being genotoxic and there is evidence that E171 administration exacerbates colon tumor formation in murine models. However, less is known about the effects of E171 accumulation once the exposure stopped, then we hypothesized that toxic effects could be detected even after E171 removal. Therefore, we investigated the effects of E171 exposure after being removed from colon cell cultures. Human colon cancer cell line (HCT116) was exposed to 0, 1, 10 and 50 μg/cm of E171. Our results showed that in the absence of cytotoxicity, E171 was accumulated in the cells after 24 of exposure, increasing granularity and reactive oxygen species, inducing alterations in the molecular pattern of nucleic acids and lipids, and causing nuclei enlargement, DNA damage and tubulin depolymerization. After the removal of E171, colon cells were cultured for 48 h more hours to analyze the ability to restore the previously detected alterations. As we hypothesized, the removal of E171 was unable to revert the alterations found after 24 h of exposure in colon cells. In conclusion, exposure to E171 causes alterations that cannot be reverted after 48 h if E171 is removed from colon cells.
食品级二氧化钛（E171）是最常用的含纳米颗粒的食品添加剂之一。最近，欧洲食品安全局表示，由于 E171 可能具有遗传毒性，不能再将其视为安全的食品添加剂，并且有证据表明，E171 的给药会加剧小鼠模型中的结肠肿瘤形成。然而，对于 E171 暴露停止后其积累的影响知之甚少，因此我们假设即使在去除 E171 后也能检测到毒性作用。因此，我们研究了从结肠细胞培养物中去除 E171 后的暴露影响。用人结肠癌细胞系（HCT116）暴露于 0、1、10 和 50μg/cm 的 E171。我们的结果表明，在没有细胞毒性的情况下，E171 在暴露 24 小时后在细胞中积累，增加了颗粒度和活性氧，诱导核酸和脂质分子模式的改变，并导致核增大、DNA 损伤和微管蛋白解聚。去除 E171 后，再培养结肠细胞 48 小时，以分析恢复先前检测到的改变的能力。正如我们假设的那样，去除 E171 后不能逆转在结肠细胞中暴露 24 小时后发现的改变。总之，如果从结肠细胞中去除 E171，则暴露于 E171 会导致改变，并且在 48 小时后无法逆转。
