Details:

Alternative Title:
NanoImpact
Personal Author:
Stueckle, Todd A. ; Davidson, Donna C. ; Derk, Raymond ; Kornberg, Tiffany G. ; Schwegler-Berry, Diane ; ... More +
Stueckle, Todd A. ; Davidson, Donna C. ; Derk, Raymond ; Kornberg, Tiffany G. ; Schwegler-Berry, Diane ; Pirela, Sandra V. ; Deloid, Glen ; Demokritou, Philip ; Luanpitpong, Sudjit ; Rojanasakul, Yon ; Wang, Liying Less -
Description:
With rapid development of novel nanotechnologies that incorporate engineered nanomaterials (ENMs) into manufactured products, long-term, low dose ENM exposures in occupational settings is forecasted to occur with potential adverse outcomes to human health. Few ENM human health risk assessment efforts have evaluated tumorigenic potential of ENMs. Two widely used nano-scaled metal oxides (NMOs), cerium oxide (nCeO|) and ferric oxide (nFe|O|) were screened in the current study using a sub-chronic exposure to human primary small airway epithelial cells (pSAECs). Multi-walled carbon nanotubes (MWCNT), a known ENM tumor promoter, was used as a positive control. Advanced dosimetry modeling was employed to ascertain delivered | administered dose in all experimental conditions. Cells were continuously exposed | to deposited doses of 0.18 μg/cm| or 0.06 μg/cm| of each NMO or MWCNT, respectively, over 6 and 10 weeks, while saline- and dispersant-only exposed cells served as passage controls. Cells were evaluated for changes in several cancer hallmarks, as evidence for neoplastic transformation. At 10 weeks, nFe|O|- and MWCNT-exposed cells displayed a neoplastic-like transformation phenotype with significant increased proliferation, invasion and soft agar colony formation ability compared to controls. nCeO|-exposed cells showed increased proliferative capacity only. Isolated nFe|O| and MWCNT clones from soft agar colonies retained their respective neoplastic-like phenotypes. Interestingly, nFe|O|-exposed cells, but not MWCNT cells, exhibited immortalization and retention of the neoplastic phenotype after repeated passaging (12 - 30 passages) and after cryofreeze and thawing. High content screening and protein expression analyses in acute exposure ENM studies | immortalized nFe|O| cells, and isolated ENM clones, suggested that long-term exposure to the tested ENMs resulted in iron homeostasis disruption, an increased labile ferrous iron pool, and subsequent reactive oxygen species generation, a well-established tumorigenesis promotor. In conclusion, sub-chronic exposure to human pSAECs with a cancer hallmark screening battery identified nFe|O| as possessing neoplastic-like transformation ability, thus suggesting that further tumorigenic assessment is needed.
Subject:
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Article
Iron Homeostasis
Nano-scaled Metal Oxide
Nanomaterial
Neoplastic Transformation
Tumorigenesis

Source:
NanoImpact. 6:39-54
Pubmed ID:
28367517
Pubmed Central ID:
PMC5372702
Document Type:
Journal Article
Funding:
R01 EB018857/EB/NIBIB NIH HHSUnited States/ ; R01 ES022968/ES/NIEHS NIH HHSUnited States/ ; T32 HL007118/HL/NHLBI NIH HHSUnited States/ ; CC999999/Intramural CDC HHSUnited States/ ; U24 ES026946/ES/NIEHS NIH HHSUnited States/
R01 EB018857/EB/NIBIB NIH HHSUnited States/ ; R01 ES022968/ES/NIEHS NIH HHSUnited States/ ; T32 HL007118/HL/NHLBI NIH HHSUnited States/ ; CC999999/Intramural CDC HHSUnited States/ ; U24 ES026946/ES/NIEHS NIH HHSUnited States/ Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:1ed860644d0c138f94cce839ed5bcaffb210c0c4d28cdb935b4785d33f32ced3
File Type:

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