Acute and long-term in vitro effects of zinc oxide nanoparticles

Abstract

Since most of the toxic studies of zinc oxide nanoparticles (ZnO NPs) focused on acute and high-dose exposure conditions, the aim of the present study was to fill the existing knowledge gap of long-term effects of ZnO NPs at sub-toxic doses. To overcome this point, we have evaluated the toxic, genotoxic, and carcinogenic effects of ZnO NPs under long-term treatments (12 weeks), using a sub-toxic dose (1 µg/mL) according to acute 48-h exposure. Preliminarily, oxidative stress and genotoxic/oxidative DNA damage were determined under acute exposure and high-dose conditions. To determine the role of oxidative DNA damage, a wild-type mouse embryonic fibroblast (MEF Ogg1 (+/+)) and its isogenic 8-oxo-guanine DNA glycosylase 1 (Ogg1) knockout partner (MEF Ogg1 (-/-)) cell lines were used. Although short-term exposure (24-h) experiments demonstrated that ZnO NPs were able to induce ROS, genotoxicity, and oxidative DNA damage in both cell lines, no effects were obtained under long-term exposure scenario. Thus, 1 µg/mL exposure over 12 weeks was unable to induce genotoxicity as well as cellular transformation in both cell types, as indicated by the lack of observed morphological cell changes, variations in the secretion of matrix metalloproteinases, and anchorage-independent cell growth ability, regarded as cancer-like phenotypic hallmarks. Our results indicate that short-term effects of ZnO NP exposure are not replicated under long-term and sub-toxic dose conditions. All together, the lack of genotoxic/carcinogenic effects after chronic treatments seem to indicate a reduced risk associated with ZnO NP exposure.

Micronuclei Detection by Flow Cytometry as a High-Throughput Approach for the Genotoxicity Testing of Nanomaterials

“…Nevertheless, neither of the reported studies proved the ability of Zn ions to produce MN. Hence, we propose that the ions release would explain the in general controversial data reported when the genotoxicity of ZnONPs is evaluated after acute exposures, the negative effects observed after long-term exposures [43] and the negative effects observed in in vivo studies. Furthermore, as it is well known, ZnONPs are highly cytotoxic which could mask a genotoxic response [44,45].…”

“…Nevertheless, positive effects were found in Caco-2 cells [41] and in human THP1 monocytic cells [42] by using the CBMN assay. This genotoxic effect was attributed to their ability to induce reactive oxygen species (ROS) [41][42][43], generating an inflammatory response [42]. ZnONPs dissolve quickly in both culture medium and intracellularly and after 48 h more than 80% of the ZnONPs dissolve to their ionic form [43].…”

“…This genotoxic effect was attributed to their ability to induce reactive oxygen species (ROS) [41][42][43], generating an inflammatory response [42]. ZnONPs dissolve quickly in both culture medium and intracellularly and after 48 h more than 80% of the ZnONPs dissolve to their ionic form [43]. Nevertheless, neither of the reported studies proved the ability of Zn ions to produce MN.…”

Size Dependent Uptake and Hemolytic Effect of Zinc Oxide Nanoparticles on Erythrocytes and Biomedical Potential of ZnO-Ferulic acid Conjugates

“…Though, ZnONPs have pervasive application in various medical fields, its toxicity has been highest concern and important focus. Although, acute and chronic neurotoxic, genotoxic effects of ZnONPs were demonstrated in time and concentration-dependent manner using in vitro and in vivo models 10, 11 , biocompatibility and intrinsic hemolytic activity of ZnONPs remains to be elucidated.…”

ZnO nanoparticle tracking from uptake to genotoxic damage in human colon carcinoma cells

“…Yet, a complete understanding of the cell toxicity mechanism is still to be achieved. Numerous studies have focused on oxidative stress and its key role in the cell damage (Annangi et al, 2015;Saptarshi et al, 2015), but the effective role of nanoparticles dissolution, and which physico-chemical properties of ZnO nanoparticles are responsible for oxidative stress generation is still unclear. Most researchers attribute a key role to ion release from ZnO nanoparticles in oxidative stress induction (Buerki-Thurnerr et al, 2013;Song et al, 2010;Xia et al, 2008).…”