Mutagenicity of ZnO nanoparticles in mammalian cells: Role of physicochemical transformations under the aging process

Abstract

Zinc oxide nanoparticles (ZnO NPs) potentially undergo physicochemical transformation in the environment, which may lead to unexpected environmental and health risks. The "aging" process is essential for better understanding the toxicity and fate of NPs in the environment. However, the mutagenic effects of aged ZnO NPs are still unexplored. The present study focused on investigating the physicochemical transformation during aging process and clarifying the mutagenicity of naturally aged ZnO NPs in human-hamster hybrid (AL) cells. It was found that ZnO NPs underwent sophisticated physicochemical transformations with aging regardless of original morphology or size, such as the microstructural changes, the formation of hydrozincite (Zn5(CO3)2(OH)6) and the release of free zinc ions. Interestingly, the aged ZnO NPs were investigated to be able to result in much lower cytotoxicity while relatively high degree mutation than fresh ZnO NPs. With characterization of the soluble and insoluble fractions of aged ZnO NPs suspension, together with the control measurements using metal chelator (TPEN) and endocytosis inhibitor (Nystatin), it was revealed that the release of zinc ions and nanoparticle uptake made significantly different contributions to the mutagenicity of fresh and aged ZnO NPs. This study clearly demonstrated that the physicochemical transformation of ZnO NPs with aging plays important and comprehensive roles in the ZnO NPs-induced mutagenicity in mammalian cells.

Zinc oxide nanoparticles induced gene mutation at the HGPRT locus and cell cycle arrest associated with apoptosis in V‐79 cells

“…In spite of, the untreated control cells dying due to the toxicity of 6‐TG, because of functional HGPRT. This is consistent with previous studies of ZnO NP mutagenicity in human‐hamster hybrid (AL) cells (Wang et al, ).…”

Natural Transformation of Zinc Oxide Nanoparticles and Their Cytotoxicity and Mutagenicity

“…In addition, NP aging (weathering) affects dissolution and reactivity [13,44,45]. Previously, we reported that ZnO NPs undergo a dramatic physicochemical transformation with aging [22]. Here, we confirm a similar transformation process and the neoformation of Zn 5 (CO 3 ) 2 (OH) 6 (Figure 1).…”

“…It is possible that the mechanisms underlying ZnO NP cytotoxicity differ from those underlying ZnO NP mutagenicity. Previously, we revealed that, during the aging process, Zn 2+ ions and solid particles contribute differently to the mutagenicity of ZnO NPs [22]. These observations indicate that the mechanisms of ZnO NP toxicity are complicated and more studies focusing on mutagenicity and NP transformations in the environment are needed.…”

“…For example, recent studies have shown that dissolution converts ZnO NPs into Zn 2+ under suitable pH environments [17,18]. Also, newly formed products such as hydrozincite (Zn 5 (CO 3 ) 2 (OH) 6 ), smithsonite (ZnCO 3 ), and zinc sulfide (ZnS) are possible in the presence of an appropriate concentration of carbonate and sulfide and under suitable pH conditions [19][20][21][22][23]. An increasing number of studies have shown that ZnO NPs induce various toxic effects, including cytotoxicity, genotoxicity, inflammation, and oxidative stress [12,[24][25][26][27][28].…”

Managing Risk in Nanotechnology

“…monthly) re-testing of parameters such as size distribution to ensure relevance of the characterisation data to the toxicity data (Izak-Nau et al, 2015 ). Similar impacts of ageing (in Milli Q water) of Zinc oxide NMs on the mutagenicity of the NMs to human-hamster hybrid (AL) cells were found, whereby the ZnO NMs underwent sophisticated physicochemical transformations with aging such as microstructural changes, the formation of hydrozincite (Zn 5 (CO 3 ) 2 (OH) 6 ) and the release of free zinc ions (Wang et al, 2015 ). Interestingly, the aged ZnO NMs resulted in much lower cytotoxicity but a relatively higher degree of mutation than fresh ZnO NMs (Wang et al, 2015 ).…”