Many engineered nanomaterials (ENMs) do not elicit detectable cytotoxicity using traditionally developed methods for bulk materials or chemicals, due to the low sensitivity of the methods. Thus, more sensitive methodologies are needed to evaluate their safety profiles. DNA methylation is an early sensitive parameter in response to a wide range of exogenous and endogenous stimuli including ENMs. However, there is limited understanding on this front, and, to address this issue, we performed DNA methylation sequencing at base-pair resolution in lung A549 and kidney HEK293T cells upon diverse ENM exposure. Exposure of silver nanoparticles and graphene oxide led to significant increases in global 5-mC level, which was however to a much less extent for gold nanoparticles, carbon nanotubes, nano-TiO<sub>2</sub> and nano-ZnO. Furthermore, physicochemical properties, such surface modification, affected ENM-induced DNA methylation variations. Through gene functional mapping, significant perturbations in cellular processes and signaling pathways could be ascribed primarily to DNA methylation alterations. Supported by gene expression and toxicological/physiological evaluations, adverse outcome pathways, adaptive cell survival and compensatory effects were identified due to the genome-wide DNA methylation changes. Thus, ENM-induced DNA methylation variations represent a more sensitive fingerprint analysis of their direct and indirect effects that may be overlooked by the traditional toxicity assays, and the understanding on the structure-activity relationship for DNA methylation changes induced by ENMs would open a new avenue for their safer design.<br/>

Genome-wide DNA methylation variations upon engineered nanomaterials and their implications in nanosafety assessment

253rd National Meeting (2017)

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