Neurotoxic effects of trimethyltin and triethyltin on human fetal neuron and astrocyte cultures: a comparative study with rat neuronal cultures and human cell lines.
Trimethyltin (TMT) and triethyltin (TET) caused cell death in cultures of primary human neurons and astrocytes, rat neurons and human neuroblastoma cell lines. Human neurons and astrocytes showed a delayed response to TMT cytotoxicity. After 24h of TMT exposure, LC50 values were 148.1, 335.5 and 609.7 microM for SK-N-MC neuroblastoma cell line, neurons and astrocytes, respectively. Over 5 days of exposure, the cytotoxic potency of TMT increased about 70-fold in human cortical neurons. Rat hippocampal neurons were the most vulnerable cells to TMT cytotoxicity, exhibiting an LC50 value 30-fold lower (1.4 microM) than that of rat cerebellar granule cells (44.28 microM). With the exception of rat hippocampal neurons, TET was more potent than TMT in inducing cell death (LC50 values of 3.5-16.9 microM). Moreover, TET was more effective than TMT in increasing intracellular free Ca2+ concentration in human and rat neurons. This work shows that human fetal neuron and astrocyte cultures are a useful model for studying the neurotoxic effects of these environmental contaminants and, thus, predicting their impact on human health.
Department of Pharmacology and Toxicology, Institut d'Investigacions Biomèdiques de Barcelona, CSIC, IDIBAPS, Rosselló 161, Barcelona E-08034, Spain. rcmfat@iibb.csic.es
Rosa M
RM
Cristòfol
Sergi
S
Gassó
David
D
Vílchez
María
M
Pertusa
Eduardo
E
Rodríguez-Farré
Coral
C
Sanfeliu
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005333:Fetus / Q000166:cytology; D006801:Humans; D008297:Male; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D014267:Triethyltin Compounds / Q000633:toxicity*; D014298:Trimethyltin Compounds / Q000633:toxicity*
D014267:Triethyltin Compounds; D014298:Trimethyltin Compounds; C046488:trimethyltin; C031575:triethyltin; D002118:Calcium