Nanoceria, Alone or in Combination with Cigarette-Smoke Condensate, Induce Transforming and Epigenetic Cancer-Like Features In Vitro

Abstract

Aim: To detect cell transformation effects of nanoceria after long-term exposure (up to 6 weeks) and to determine their potential interactions with cigarette smoke condensate, as a model of environmental carcinogenic pollutant. Materials & methods: Human bronchial epithelial BEAS-2 cells were used to determine transformation effects (invasion and tumorspheres induction), as well as changes in the expression of a battery of miRNAs related to the carcinogenesis process. Results: Nanoceria- and co-exposed cells exhibit cell transforming potential, with significantly increased invasion and tumorsphere formation abilities. Likewise, these exposures produced a high impact on the battery of miRNAs used. Conclusion: Nanoceria exposure induces cell-transformation and shows a positive interaction with the cell-transforming effects of cigarette smoke condensate. Besides, cerium dioxide nanoparticles and the co-exposure produced potential toxicity at the transcriptome level, which is related to tumorigenesis.

MicroRNAs as a Suitable Biomarker to Detect the Effects of Long-Term Exposures to Nanomaterials. Studies on TiO2NP and MWCNT

“…An additional advantage of in vitro long-term exposure systems is that they permit the detection of different long-term effects, such as those related to the acquisition of a tumoral phenotype. Indeed, the cell-transformation ability of different NMs has already been reported using these experimental approaches, as demonstrated with cobalt nanoparticles [4], titanium dioxide nanoparticles [19], multiwalled carbon nanotubes [20], nickel oxide nanoparticles [26], and cerium oxide [15].…”

“…Thus, mouse embryonic fibroblast knockouts for the Ogg1 gene (MEF Ogg1 −/− cells; gift from Dr. Deborah Barnes at Cancer Research UK, UK) previously exposed for 12 weeks to 1 µg/mL of zinc oxide nanoparticles (ZnONP) and to 0.1 µg/mL of cobalt nanoparticles (CoNP) were used [4,5]. In addition, BEAS-2B cells previously exposed for 6 weeks to mesoporous silica nanoparticles (MSiNP) at 10 µg/mL (unpublished results) and cerium dioxide nanoparticles (CeO 2 NP) at 2.5 µg/mL [15] were included. Longterm cell culture conditions and miRNA analysis were conducted, as reported in the previous sections.…”

“…This indicates that initiation, proliferation, and control of the apoptotic program of tumor cells are modulated by different epigenetic entities, including miRNAs [14]. In this direction, we have recently shown that following long-term exposure to nanoceria, bronchial epithelial BEAS-2B cells acquire an oncogenic phenotype characterized by an increased cell-invasion capacity and tumorsphere-formation ability [15]. Interestingly, we demonstrated that these oncogenic changes were accompanied by altered expression of several miRNAs with known roles in the carcinogenesis process [15].…”

“…This study moves one step further than the previous one [15] by identifying a reduced set of informative miRNAs useful in detection of potential oncogenic effects induced by NM exposures. Since miRNAs participate in many overlapping cellular processes, the miRNA-level changes of the proposed set can also be conceived as more general biomarkers for toxicological assessment of NMs under scenarios of long-term exposure.…”

“…In this direction, we have recently shown that following long-term exposure to nanoceria, bronchial epithelial BEAS-2B cells acquire an oncogenic phenotype characterized by an increased cell-invasion capacity and tumorsphere-formation ability [15]. Interestingly, we demonstrated that these oncogenic changes were accompanied by altered expression of several miRNAs with known roles in the carcinogenesis process [15]. More specifically, expression levels of about the 30% of an initial panel of 33 candidates showed relevant changes, which included miRNAs considered oncogenes (OncomiRs) or tumor suppressors (Anti-OncomiRs), based on whether they target tumor suppressor genes or oncogenes, respectively [16].…”