Science Inventory

Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc


Currier, J., W. Cheng, R. Conolly, AND B. Chorley. Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc. Society of Toxicology, San Diego, CA, March 22 - 26, 2015.


To be presented at the annual Society of Toxicology Meeting


Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung in environmental settings, which has been linked to various adverse health effects. Here, we further elucidate both the adaptive and adverse cellular responses of a normal human bronchial epithelial cell line (BEAS-2B) to zinc exposure in vitro. BEAS-2B cells were exposed to Zn2+ with 1 µM pyrithione, an ionophore that facilitates cellular uptake, for up to 48 h. Cytotoxicity was characterized by examining ATP levels with the CellTiter-Glo assay. Additionally, intracellular levels of Bak and Lamin B, markers of apoptosis, were quantitatively determined. Zn2+ exposure elicited a dose and time-dependent reduction in ATP levels compared with unexposed cells. After 24 h, markedly reduced viability was observed in cells treated with 5 (71±3%) and 7 (19±4%) µM Zn2+, but not cells exposed to 1 (88±2%) or 3 (94±2%) µM Zn2+ when compared with unexposed cells. Viability was further reduced in cells exposed to 3 µM Zn2+ after 48 h to 31±5%, however, cells exposed to 1 µM Zn2+ were not affected. After 24 hours, Bak and Lamin B levels increased from 17 and 10 ng/mL, respectively, in control cells to 38 and 25 ng/mL in cells exposed to 3 µM Zn2+. These levels increased further after 40 h to 67 and 30 ng/mL, but decreased to 49 and 26 ng/mL after 48 h of exposure. In agreement with the Bak and Lamin B levels, a portion of the cells treated with 3 µM appeared to recover. Visual inspection indicated that cells returned to a flattened, attached morphology between 40 and 48 h. These data suggest that the switch between adaptation and apoptosis in our model begins to occur at exposures of approximately 3 µM Zn2+ and as early as 24 h after exposure. Future work will determine the genomic response that mediates this switch, including the characterization of NRF2 and p53 pathway activation. This abstract does not necessarily reflect the policy of the US EPA.



Record Details:

Product Published Date: 03/26/2015
Record Last Revised: 04/22/2015
OMB Category: Other
Record ID: 307776