Darne Christian, Coulais Catherine, Terzetti Francine, Fontana Caroline, Binet Stéphane, Gaté Laurent, Guichard Yves
Département Toxicologie et Biométrologie, Institut National de Recherche et de Sécurité (INRS), Rue du Morvan, CS 60027, 54519 Vandoeuvre Les Nancy Cedex, France.
Département Toxicologie et Biométrologie, Institut National de Recherche et de Sécurité (INRS), Rue du Morvan, CS 60027, 54519 Vandoeuvre Les Nancy Cedex, France.
Mutat Res Genet Toxicol Environ Mutagen. 2016 Jan 15;796:23-33. doi: 10.1016/j.mrgentox.2015.11.012. Epub 2015 Nov 27.
Crystalline silica particles and asbestos have both been classified as carcinogenic by the International Agency for Research on Cancer (IARC). However, because of the limited data available, amorphous silica was not classifiable. In vitro, the carcinogenic potential of natural crystalline and amorphous silica particles has been revealed by the Syrian Hamster Embryo (SHE) cell transformation assay. On the other hand, the genotoxic potential of those substances has not been investigated in SHE cells. And yet, genotoxicity assays are commonly used for hazard evaluation and they are often used as in vitro assays of reference to predict a possible carcinogenic potential. The main objective of this study was to compare the genotoxic potential and the carcinogenic potential of different crystalline and amorphous silica particles in SHE cells. Three silica samples of different crystallinity were used: natural amorphous silica, partially crystallized silica and quartz silica particles. Their genotoxicity were tested through the in vitro micronucleus assay and the comet assay in SHE, and their carcinogenic potential through the SHE transformation assay. In addition, silica samples were also tested with the same genotoxicity assays in V79 hamster-lung cells, a common in vitro model for particle exposure. Results obtained in the micronucleus and the comet assays show that none of the silica was capable of inducing genotoxic effects in SHE cells and only the amorphous silica induced genotoxic effects in V79 cells. However in the SHE cell transformation assays, the partially crystallized and quartz silica were able to induce morphological cell transformation. Together, these data suggest that, in vitro, the short-term genotoxic assays alone are not sufficient to predict the hazard and the carcinogenic potential of this type of particles; SHE transformation assay appears a more reliable tool for this purpose and should be included in the "in vitro battery assays" for hazard assessment.
结晶二氧化硅颗粒和石棉均已被国际癌症研究机构(IARC)列为致癌物。然而,由于可用数据有限,无定形二氧化硅无法进行分类。在体外,叙利亚仓鼠胚胎(SHE)细胞转化试验揭示了天然结晶和无定形二氧化硅颗粒的致癌潜力。另一方面,尚未在SHE细胞中研究这些物质的遗传毒性潜力。然而,遗传毒性试验通常用于危害评估,并且它们经常被用作预测可能致癌潜力的体外参考试验。本研究的主要目的是比较不同结晶和无定形二氧化硅颗粒在SHE细胞中的遗传毒性潜力和致癌潜力。使用了三种不同结晶度的二氧化硅样品:天然无定形二氧化硅、部分结晶二氧化硅和石英二氧化硅颗粒。通过体外微核试验和彗星试验在SHE中测试它们的遗传毒性,并通过SHE转化试验测试它们的致癌潜力。此外,还在V79仓鼠肺细胞(一种常见的颗粒暴露体外模型)中使用相同的遗传毒性试验对二氧化硅样品进行了测试。微核试验和彗星试验的结果表明,没有一种二氧化硅能够在SHE细胞中诱导遗传毒性效应,只有无定形二氧化硅在V79细胞中诱导了遗传毒性效应。然而,在SHE细胞转化试验中,部分结晶二氧化硅和石英二氧化硅能够诱导细胞形态转化。总之,这些数据表明,在体外,仅短期遗传毒性试验不足以预测这类颗粒的危害和致癌潜力;SHE转化试验似乎是用于此目的的更可靠工具,应纳入“体外试验组合”以进行危害评估。