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- Title
Biomarkers of Exposure and Effect in Human Lymphoblastoid TK6 Cells Following [13C2]-Acetaldehyde Exposure.
- Authors
Moeller, Benjamin C.; Recio, Leslie; Green, Amanda; Sun, Wei; Wright, Fred A.; Bodnar, Wanda M.; Swenberg, James A.
- Abstract
Editor’s Highlight: Byproducts of constitutive metabolism may themselves be toxic, complicating the risk assessment of the same chemicals encountered from external sources. The application of stable labeled compounds offers insight into the source of chemicals producing biological effects and provides a basis to quantify the contribution of exogenous exposure to biological events. This report describes the concentration dependent contributions of exogenous [13C2]-acetaldehyde and endogenously produced acetaldehyde to adduct formation in human lymphoblastoid cells in vitro. — Jeffrey FisherThe dose-response relationship for biomarkers of exposure (N2-ethylidene-dG adducts) and effect (cell survival and micronucleus formation) was determined across 4.5 orders of magnitude (50nM–2mM) using [13C2]-acetaldehyde exposures to human lymphoblastoid TK6 cells for 12h. There was a clear increase in exogenous N2-ethylidene-dG formation at exposure concentrations ≥ 1µM, whereas the endogenous adducts remained nearly constant across all exposure concentrations, with an average of 3.0 adducts/107 dG. Exogenous adducts were lower than endogenous adducts at concentrations ≤ 10µM and were greater than endogenous adducts at concentrations ≥ 250µM. When the endogenous and exogenous adducts were summed together, statistically significant increases in total adduct formation over the endogenous background occurred at 50µM. Cell survival and micronucleus formation were monitored across the exposure range and statistically significant decreases in cell survival and increases in micronucleus formation occurred at ≥ 1000µM. This research supports the hypothesis that endogenously produced reactive species, including acetaldehyde, are always present and constitute the majority of the observed biological effects following very low exposures to exogenous acetaldehyde. These data can replace default assumptions of linear extrapolation to very low doses of exogenous acetaldehyde for risk prediction.
- Subjects
PHYSIOLOGICAL effects of acetaldehyde; BIOMARKERS; LYMPHOBLASTOID cell lines; DNA adducts; NUCLEOLUS; EXTRAPOLATION
- Publication
Toxicological Sciences, 2013, Vol 133, Issue 1, p1
- ISSN
1096-6080
- Publication type
Article
- DOI
10.1093/toxsci/kft029