PMID- 8396389 OWN - NLM STAT- MEDLINE DCOM- 19931005 LR - 20190904 IS - 0340-5761 (Print) IS - 0340-5761 (Linking) VI - 67 IP - 5 DP - 1993 TI - Effects of cisplatin and ORG.2766 in chick embryonic brain cell cultures. PG - 325-9 AB - The neurotoxicity of cisplatin and ORG.2766, both separately and in combination, was investigated using serum-free chick embryonic brain cell cultures. At low cisplatin concentrations glial cells were affected more than nerve cells. The onset of cisplatin toxicity was delayed, the major effects only being seen after the treatment was finished and when no free cisplatin was present in the culture medium. The data further indicate that the area under the graph of free cisplatin concentration in the culture medium against time (AUC) is a measure of cisplatin toxicity. The AUC of free cisplatin in the culture medium which causes a 50% reduction in the expression of glial fibrillary associated protein (GFAP) was similar to blood AUC values in humans known to induce neurotoxic effects in around 80% of patients. ORG.2766 at very high concentrations increased lysosomal activity, as measured by neutral red uptake, and the expression of GFAP. ORG.2766 did not influence the toxicity of cisplatin in culture. FAU - Bruinink, A AU - Bruinink A AD - Institute of Toxicology, Swiss Federal Institute of Technology, Schwerzenbach. FAU - Birchler, F AU - Birchler F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Arch Toxicol JT - Archives of toxicology JID - 0417615 RN - 0 (Antineoplastic Agents) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Peptide Fragments) RN - 50913-82-1 (Org 2766) RN - 9002-60-2 (Adrenocorticotropic Hormone) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Adrenocorticotropic Hormone/*analogs & derivatives/pharmacology MH - Animals MH - Antineoplastic Agents/*pharmacology MH - Brain/*cytology/drug effects MH - Cell Differentiation/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Chick Embryo MH - Cisplatin/*antagonists & inhibitors/pharmacokinetics/toxicity MH - Glial Fibrillary Acidic Protein/biosynthesis MH - Half-Life MH - Lysosomes/drug effects MH - Neuroglia/drug effects MH - Neurons/drug effects MH - Peptide Fragments/*pharmacology EDAT- 1993/01/01 00:00 MHDA- 1993/01/01 00:01 CRDT- 1993/01/01 00:00 PHST- 1993/01/01 00:00 [pubmed] PHST- 1993/01/01 00:01 [medline] PHST- 1993/01/01 00:00 [entrez] AID - 10.1007/BF01973703 [doi] PST - ppublish SO - Arch Toxicol. 1993;67(5):325-9. doi: 10.1007/BF01973703.