Toxicity of anticancer agents on normal neural cells during chemotherapy of primary or secondary brain tumors is a clinical problem of increasing relevance and concern. In this perspective, here we used primary cultures of rat cortical microglia as an in vitro paradigm of normal glia to investigate the neurotoxicity of anticancer agents. The effects of two compounds frequently used for treatment of brain tumors, methotrexate (MTX) and temozolomide (TMZ), were compared to those of a known microglial activator, bacterial lipopolysaccharide (LPS); cell viability and metabolism was assessed by the MTS assay. We found that LPS, in the low-intermediate range of concentrations, strongly activates microglia cells, but a highly significant decrease in viabilitywas observed from 100 ng/ml onward.TMZhas no effect at concentrations of clinical interest, whereasMTX significantly increases cell metabolism at 30 microM, a phenomenon possibly reflecting MTX neurotoxicity observed in patients.
Vairano, M., Graziani, G., Tentori, L., Tringali, G., Navarra, P., Dello Russo, C. (2004). Primary cultures of microglial cells for testing toxicity of anticancer drugs. TOXICOLOGY LETTERS, 148, 91-94 [10.1016/j.toxlet.2003.12.058].
Primary cultures of microglial cells for testing toxicity of anticancer drugs.
GRAZIANI, GRAZIA;TENTORI, LUCIO;
2004-01-01
Abstract
Toxicity of anticancer agents on normal neural cells during chemotherapy of primary or secondary brain tumors is a clinical problem of increasing relevance and concern. In this perspective, here we used primary cultures of rat cortical microglia as an in vitro paradigm of normal glia to investigate the neurotoxicity of anticancer agents. The effects of two compounds frequently used for treatment of brain tumors, methotrexate (MTX) and temozolomide (TMZ), were compared to those of a known microglial activator, bacterial lipopolysaccharide (LPS); cell viability and metabolism was assessed by the MTS assay. We found that LPS, in the low-intermediate range of concentrations, strongly activates microglia cells, but a highly significant decrease in viabilitywas observed from 100 ng/ml onward.TMZhas no effect at concentrations of clinical interest, whereasMTX significantly increases cell metabolism at 30 microM, a phenomenon possibly reflecting MTX neurotoxicity observed in patients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
