Trimethyltin reduces ATP levels and MTT reduction in the LRM55 rat astrocytoma cell line.
The LRM55 rat astrocytoma cell line was used to study the time and concentration effects of trimethyltin (TMT) exposure on intracellular adenosine triphosphate (ATP) levels, formazan production from (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and lactate dehydrogenase (LDH) release. TMT concentrations of > or =50 microM produced a delayed increase in extracellular LDH from approximately 20% at 24 h to almost 70%, at 72 h. Twenty-four hours before cell lysis was detectable ATP levels decreased to less than 30% and formazan production declined to 70% (50 microM), 31% (100 microM), and 21% (200 microM) of control values. Concentrations of TMT (5 and 10 microM) that produced little or no LDH release also decreased ATP levels (62 and 49% of control, respectively) and formazan production (63 and 52% of control, respectively) by 48 h. These data support the hypothesis that TMT exposure interferes with energy production and that this event likely contributes to the delayed cell death seen in this cell line. Moreover, the declines in ATP and formazan production can occur at subtoxic concentrations in LRM55 cells.
Eyer
C L
CL
Department of Pharmaceutical Sciences, The University of Montana, Missoula, MT 59812, USA. eyer@selway.umt.edu
Rio
C
C
Smith
J R
JR
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D001254:Astrocytoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004396:Coloring Agents / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D013778:Tetrazolium Salts / Q000378:metabolism*; D013844:Thiazoles / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014298:Trimethyltin Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D014298:Trimethyltin Compounds; C046488:trimethyltin; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue