Luo YS, Furuya S, Chiu W, Rusyn I. Characterization of inter-tissue and inter-strain variability of TCE glutathione conjugation metabolites DCVG, DCVC, and NAcDCVC in the mouse.
J Toxicol Environ Health A. 2018;81(1-3):37-52. doi: 10.1080/15287394.2017.1408512. Epub 2017 Nov 30.
Yu-Syuan Luo Texas A&M University, College Station, TX|
Nan-Hung Hsieh Texas A&M University, College Station, TX
Ivan Rusyn Texas A&M University, College Station, TX
|Contact||Ivan Rusyn IRusyn@cvm.tamu.edu
|Phenotype archive study|
|MPD identifiers||Rusyn10 MPD:617|
|No updates/corrections. Initial release date: 04/2018.|
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Purpose: The qualitative and quantitative similarities in metabolism of trichloroethylene (TCE) and tetrachloroethylene (aka perchloroethylene; PERC or PCE) were examined in male mice from C57BL/6/J, B6C3F1/J, and NZW/LacJ strains. PERC-relevant data can be found in Rusyn11. Mice were orally administered a molar-equivalent, single dose of TCE or PERC (6 mmole/kg) or vehicle, and sacrificed at various time points up to 36 hours. Levels of parent compounds (TCE or PERC), oxidative metabolites (TCA and/or TCOH), and glutathione conjugation metabolites (D/TCVG, D/TCVC, NAcD/TCVC) were measured in serum, liver, kidney, brain, and lung.
Methods: See Luo et al., 2018 for details (manuscript in preparation).
Chemicals: Trichloroethylene (TCE; PN: 24254, â¥ 99.0%) and tetrachloroethylene (PERC; PN: 270393, â¥ 99.9%) were purchased from Sigma Aldrich, St. Louis MO USA.
Mice: Adult male mice (6-7 weeks of age) were obtained from the Jackson laboratory (Bar Harbor ME). Animals were housed in polycarbonate cages on Sani-Chips irradiated hardwood bedding (PJ Murphy Forest Products, Montville NJ), and fed with NTP-2000 (Zeigler Brothers, Gardners PA) wafer diet and water ad libitum on a 12h light-dark cycle.
Study design: Following one-week acclimatization period, the mice were gavaged with a molar-equivalent single dose (6 mmole/kg) of TCE or PERC in vehicle (5% Alkamuls El-620 in saline, 5 mL/kg). Mice were sacrificed at 1, 2, 6, 12, 24, 36h after dosing. Organs (liver, kidney, brain, and lung) were collected and rinsed in phosphate-buffered saline, blotted dry, weighed, and snap-frozen in liquid nitrogen. Serum was prepared using Z-gel tubes (Sarstedt, Germany) by centrifugation of blood collected from vena cava. Parent compounds and metabolites from oxidative and glutathione conjugation pathways were profiled in serum, liver, kidney, brain, and lung.
Figures for TCE:
Per animal data for TCE: