Thionate versus Oxon: comparison of stability, uptake, and cell toxicity of ((14)CH(3)O)(2)-labeled methyl parathion and methyl paraoxon with SH-SY5Y cells.
The stability, hydrolysis, and uptake of the organophosphates methyl parathion and methyl paraoxon were investigated in SH-SY5Y cells. The stabilities of ((14)CH(3)O)(2)-methyl parathion ((14)C-MPS) and ((14)CH(3)O)(2)-methyl paraoxon ((14)C-MPO) at 1 microM in culture media had similar half-lives of 91.7 and 101.9 h, respectively. However, 100 microM MPO caused >95% cytotoxicity at 24 h, whereas 100 microM MPS caused 4-5% cytotoxicity at 24 h ( approximately 60% cytotoxicity at 48 h). Greater radioactivity was detected inside cells treated with MPO as compared to MPS, although >80% of the total MPO uptake was primarily dimethyl phosphate (DMP). Maximum uptake was reached after 48 h of (14)C-MPS or (14)C-MPO exposure with total uptakes of 1.19 and 1.76 nM/10(6) cells for MPS and MPO, respectively. The amounts of MPS and MPO detected in the cytosol after 48 h of exposure time were 0.54 and 0.37 nM/10(6) cells, respectively.
Bharate
Sandip B
SB
Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, MT 59812, USA.
Prins
John M
JM
George
Kathleen M
KM
Thompson
Charles M
CM
D002250:Carbon Radioisotopes / Q000032:analysis; D045744:Cell Line, Tumor; D004355:Drug Stability; D006801:Humans; D007306:Insecticides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D007553:Isotope Labeling; D008743:Methyl Parathion / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D010261:Paraoxon / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity
D002250:Carbon Radioisotopes; D007306:Insecticides; D008743:Methyl Parathion; D010261:Paraoxon; C008480:methylparaoxon