Catalán Julia, Ilves Marit, Järventaus Hilkka, Hannukainen Kati-Susanna, Kontturi Eero, Vanhala Esa, Alenius Harri, Savolainen Kai M, Norppa Hannu
Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland; Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland; Department of Anatomy, Embryology and Genetics, University of Zaragoza, Zaragoza, Spain.
Environ Mol Mutagen. 2015 Mar;56(2):171-82. doi: 10.1002/em.21913. Epub 2014 Sep 24.
Nanocellulosics are among the most promising innovations for a wide-variety of applications in materials science. Although nanocellulose is presently produced only on a small scale, its possible toxic effects should be investigated at this early stage. The aim of the present study was to examine the potential genotoxicity and immunotoxicity of two celluloses in vitro - cellulose nanocrystals (CNC; mean fibril length 135 nm, mean width 7.3 nm) and a commercially available microcrystalline (non-nanoscale) cellulose (MCC; particle size ∼50 µm). Both celluloses showed 55% cytotoxicity at approximately 100 µg/ml after 4-h, 24-h, and 48-h treatment of human bronchial epithelial BEAS 2B cells, as determined by luminometric detection of ATP and cell count (dead cells identified by propidium iodide). Neither of the materials was able to induce micronuclei (MN) in binucleate or mononucleate BEAS 2B cells after a 48-h treatment (2.5-100 µg/ml). In human monocyte-derived macrophages, MCC induced a release (measured by enzyme-linked immunosorbent assay; ELISA) of the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and (after lipopolysaccharide-priming) interleukin 1β (IL-1β) after a 6-h exposure to a dose of 300 µg/ml, but CNC (30-300 µg/ml) did not. In conclusion, our results show that nanosized CNC is neither genotoxic nor immunotoxic under the conditions tested, whereas non-nanosized MCC is able to induce an inflammatory response. More studies are needed, especially in vivo, to further assess if CNC and other nanocelluloses induce secondary genotoxic effects mediated by inflammation.
纳米纤维素是材料科学中众多应用前景广阔的创新材料之一。尽管目前纳米纤维素仅小规模生产，但在此早期阶段就应研究其可能的毒性作用。本研究的目的是在体外检测两种纤维素——纤维素纳米晶体（CNC；平均原纤维长度135纳米，平均宽度7.3纳米）和市售微晶（非纳米级）纤维素（MCC；粒径约50微米）的潜在遗传毒性和免疫毒性。在用ATP发光检测和细胞计数（用碘化丙啶鉴定死细胞）测定时，在对人支气管上皮BEAS 2B细胞进行4小时、24小时和48小时处理后，两种纤维素在约100微克/毫升时均显示出55%的细胞毒性。在48小时处理（2.5 - 100微克/毫升）后，这两种材料均不能在双核或单核BEAS 2B细胞中诱导微核（MN）形成。在人单核细胞衍生的巨噬细胞中，MCC在暴露于300微克/毫升剂量6小时后诱导了促炎细胞因子肿瘤坏死因子α（TNF-α）的释放（通过酶联免疫吸附测定法；ELISA测量），以及（在脂多糖引发后）白细胞介素1β（IL-1β）的释放，但CNC（30 - 300微克/毫升）没有。总之，我们的结果表明，在所测试的条件下，纳米级CNC既无遗传毒性也无免疫毒性，而非纳米级MCC能够诱导炎症反应。需要更多研究，尤其是体内研究，以进一步评估CNC和其他纳米纤维素是否会诱导由炎症介导的继发性遗传毒性作用。
