Primary cultures of microglial cells for testing toxicity of anticancer drugs.
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 viability was observed from 100 ng/ml onward. TMZ has no effect at concentrations of clinical interest, whereas MTX significantly increases cell metabolism at 30 microM, a phenomenon possibly reflecting MTX neurotoxicity observed in patients.
Vairano
Mauro
M
Institute of Pharmacology, Catholic University Medical School, Largo Francesco Vito 1, Rome 00168, Italy.
Graziani
Grazia
G
Tentori
Lucio
L
Tringali
Giuseppe
G
Navarra
Pierluigi
P
Dello Russo
Cinzia
C
D000818:Animals; D000831:Animals, Newborn; D000970:Antineoplastic Agents / Q000009:adverse effects*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D018929:Cell Culture Techniques; D002470:Cell Survival; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008727:Methotrexate / Q000009:adverse effects; D017628:Microglia / Q000187:drug effects*; D009422:Nervous System Diseases / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar; D000077204:Temozolomide; D018675:Toxicity Tests / Q000379:methods
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D008070:Lipopolysaccharides; D003606:Dacarbazine; D000077204:Temozolomide; D008727:Methotrexate