Hypertrophy and increased glial fibrillary acidic protein are coupled to increased protection against cytotoxicity in glioma cell lines

This study examined the associations of increased glial fibrillary acidic protein (GFAP) levels and hypertrophic changes with susceptibility to toxic insult in C6 rat glioma cells. The cells were treated with serial pulses of dibutyryl-cAMP (dBcAMP) teach 48 hr) which increased levels of GFAP approximately twofold and the surface to volume ratio by approximately 1.7 times after the third pulse. This treatment reduced cell number by 22% and increased total protein by 10%. The cells were then exposed to different toxic substances [tin chloride, lead tetraacetate, chloroquine, cadmium chloride, aluminium chloride, mercuric chloride, acrylamide, triethyltin bromide, ethylenediaminetetraacetatic acid (EDTA)I and toxicity to the cells measured by the neutral red (NR) assay. With the exceptions of aluminium chloride and EDTA, 50% effective concentration (EC50) values for the toxic substances were increased up to 10,000 times (for cadmium chloride). Very similar increases in protection against the substances following dBcAMP treatment were found with the 1321N1 human astrocytoma cell line. We conclude that two components of gliosis, hypertrophy and increased GFAP, are associated with increased protection against a range of known neurotoxicants. (C) 1998 Elsevier Science Ltd. All rights reserved.