An in vitro model for evaluation of vaporous toxicity of trichloroethylene and tetrachloroethylene to CHO-K1 cells.
Toxicokinetics of trichloroethylene (TCE) and tetrachloroethylene (PER) in culture medium and their toxicity to CHO-K1 cells were investigated by employing an in vitro vapor exposure system. Cells were cultured in a 60 mm petri dish with a 25 mm glass dish glued in the central area. TCE or PER was added to the central glass dish so that it would evaporate and dissolve in the surrounding medium in which cells were growing. The results showed that the concentration of TCE or PER in medium increased significantly within 20 min and then decreased very rapidly with time. After a 24 h incubation, the residual of TCE or PER in the medium was very low, but was displayed in a dose-dependent manner. Treatment of cells with either TCE or PER resulted in a dose- and time-dependent inhibition of cell growth. A significantly increase in the frequency of micronuclei (MN) was also observed with either TCE or PER treatment. Low doses of TCE (5-20 microl) or PER (1-5 microl) significantly enhanced the intracellular glutathione (GSH) level. However, the level of GSH rapidly decreased with higher doses of TCE (40-80 microl) or PER (10-20 microl). Depletion of cellular GSH showed no effect on the sensitivity of cells to TCE or PER treatment. GSH-conjugation has been proposed as an activation mechanism to account for the nephrotoxicity of TCE and PER, however the toxicity of TCE and PER to CHO-K1 cells is probably mediated through a distinct mechanism.
Wang
J L
JL
Department of Chemistry, National Central University, Chung-li, 32054, Taoyuan, Taiwan, ROC.
Chen
W L
WL
Tsai
S Y
SY
Sung
P Y
PY
Huang
R N
RN
D000818:Animals; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects*; D006224:Cricetinae; D003470:Culture Media / Q000737:chemistry; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D015162:Micronucleus Tests; D012997:Solvents / Q000633:toxicity; D013750:Tetrachloroethylene / Q000494:pharmacology / Q000633:toxicity*; D014241:Trichloroethylene / Q000494:pharmacology / Q000633:toxicity*; D014835:Volatilization
D003470:Culture Media; D012997:Solvents; D014241:Trichloroethylene; D005978:Glutathione; D013750:Tetrachloroethylene