Assessment of the astrogliotic responses of three human astrocytoma cell lines to ethanol, trimethyltin chloride and acrylamide.
The astrogliotic responses of the CCF-STTG1, U251-MG, and U373-MG human astrocytoma lines were determined after exposure to ethanol, trimethyltin chloride (TMTC), and acrylamide over 4, 16, and 24h. Basal glial fibrillary acidic protein (GFAP) expression in the U-251MG and U373-MG cells was 10-fold greater than the CCF-STGG1 line. Ethanol treatment over 24h, but not at 4 and 16h, resulted in significant increases in GFAP in all three glioma lines at sub-cytotoxic levels; the GFAP responses in the CCF-STTG1 line were the most sensitive, as concentrations of 0.1 and 1mM led to increases in GFAP expression compared with control of 56.8+/-15.7 and 58.9+/-11.5%, respectively (P<0.05). Treatment with TMTC (1 microM) over 4h showed elevated GFAP expression in the U251-MG cell line to 28.0+/-15.7% above control levels (P<0.01), but not in the other U373-MG or CCF-STTG1 cells. At 4h, MTT turnover was markedly increased compared with control, particularly in the U373-MG line at concentrations as low as 1 microM (17.1+/-2.3%; P<0.01). TMTC exposure over 16 and 24h resulted in reduction in GFAP expression in all three lines at concentrations; at 24h incubation, the reduction was >50% (P<0.01). There were no changes in GFAP expression or MTT turnover in response to acrylamide except at the highest concentration ranges of 10-100 mM. This study underlines the significance of period of exposure, as well as toxin concentration in astrocytoma cellular response to toxic pressure.
Holden
Lindsay J
LJ
School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK.
Coleman
Michael D
MD
D020106:Acrylamide / Q000633:toxicity*; D001254:Astrocytoma / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology*; D002452:Cell Count; D045744:Cell Line, Tumor; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D000431:Ethanol / Q000633:toxicity*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D005911:Gliosis / Q000473:pathology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D014298:Trimethyltin Compounds / Q000633:toxicity*
D002492:Central Nervous System Depressants; D005904:Glial Fibrillary Acidic Protein; D013778:Tetrazolium Salts; D013844:Thiazoles; D014298:Trimethyltin Compounds; D020106:Acrylamide; D000431:Ethanol; D010088:Oxidoreductases; C022616:thiazolyl blue