Epigenetic mechanisms involvement in in vitro cell transformation induced by micro- and nano-silica particles

Epigenetic mechanisms that are essential in normal cell growth have been found disrupted in several human diseases such as cancer. Epigenetic mechanisms include histone post-translational modifications, DNA methylation and non-coding RNAs, which work together in order to regulate genome functions. Disruption of epigenetic machinery could lead to the modulation of gene expression, resulting in the deregulations of multiple mechanisms in cells that could be involved in the different steps of tumorigenesis. Some recent studies showed that various nanomaterials can modulate gene expression through the modulation of epigenetic marks. Despite the increasing production and utilisation of nanomaterials in various domains, their potential risk for human health is still in debates. Possible interactions between nanomaterials and epigenetic mechanisms are an important factor to take into account for their cancerogenicity evaluation.
This study is focus on two silicon dioxide particles, a crystalline silica micro-size particle (Min-U-Sil, classified as carcinogenic to human by IARC) and an amorphous silica nano-size particle (NM203). Both silica samples responded positively in the in vitro Bhas42 cell transformation assay. In the promotion condition of the assay, transformation was induced from 10 µg/cm2 and 5 µg/cm2 for Min-U-Sil and NM203, respectively. Interestingly, treatment by Min-U-Sil decreased global DNA methylation and increased expression of the both de novo DNA methyltransferases, DNMT3a and DNMT3b, in accordance with observations in cancer cells. Moreover, although a slight modification of global histone H3 and H4 acetylation status was observed after treatment, treatment by Min-U-Sil decreased the protein levels of two histone deacetylases, HDAC1 and 6, and increased HDAC2 protein level. First results obtained with NM203 indicate also epigenetic changes coming together with Bhas42 cell transformation.
In conclusion, in vitro cell transformation induced by a carcinogenic silica microparticle may involve changes in DNA methylation and protein acetylation. Such effects have to be considered in the case of silica nanoparticles.