ZnO nanoparticles and SWCNT induced general stress response pathway in HepG2 cells at non-cytotoxic doses revealed by RNA sequencing

Abstract

AbstractNanoparticles (NPs) are important in a variety of sectors, including disease diagnostics, medicine, nutrition, and many other industries. The risk of human exposure demands an early evaluation of both the basic dynamics of NPs’ interaction with biological systems and their potential consequences. Deciphering these occurrences will provide critical information regarding the health hazards and safety advantages associated with next-generation nanoformulations in clinical practice. We examined the HepG2 cell line in a systematic manner to determine the cellular response to single-walled carbon nanotubes (SWCNTs) and zinc oxide (ZnO) NPs. With the use of high-throughput transcriptomic methods, we found that both NPs induce comparable dysregulation of the endocytic and proteasomal complex genes in liver hepatocellular carcinoma cells, at levels (> 80 percent cell viability) that do not cause over-toxicity at early incubation period (6 h). SWCNT and ZnO NPs were shown to enter cells through clathrin-mediated pathways, affecting cytoskeleton gene expression, DNA damage and repair, protein ubiquitination, and cell transcriptional machinery. Our findings indicate that early response strategies activate stress-related mechanisms. Finally, this method for studying nanomaterial–cell interactions demonstrates how changes in the transcriptome profile may predict downstream consequences even at doses that do not cause acute toxicity.