In vitro assessment for neurotoxicity of antitumor agents before local administration into central nervous system.
In vitro assays for neurotoxicity with the aid of cultured mouse fetal neurons and glial cells were applied to investigate neurotoxicity of recombinant murine interferon-beta (rMuIFN-beta). These data were compared with those for MTX, ADR, and ACNU. The range of concentrations of the drugs used in these experiments spanned their clinically achievable concentrations in patient serum (IFN-beta: 1 x 10(4) IU/ml, MTX: 100 micrograms/ml, ADR: 20 micrograms/ml, ACNU: 20 micrograms/ml). rMuIFN- beta damaged both neurons and glial cells at concentrations of more than 1 x 10(5) IU/ml but did not damage them at 1 x 10(4) IU/ml or less. Microtubule-associated protein 1A (MAP1A) staining was decreased in rMuIFN-beta-treated (more than 1 x 10(5) IU/ml) neutrons. In conclusion, since IFN-beta may have some neurotoxic effects at concentrations higher than 1 x 10(5) IU/ml, it should be administered carefully, as should other antitumor agents, into the tumor cavity in the CNS following surgery.
Moriuchi
S
S
Department of Neurosurgery, Center for Adult Diseases, Osaka, Japan.
Shimizu
K
K
Miyao
Y
Y
Yamada
M
M
Ohkawa
M
M
Hayakawa
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001927:Brain Diseases / Q000139:chemically induced*; D004317:Doxorubicin / Q000633:toxicity; D005333:Fetus; D005910:Glioma / Q000188:drug therapy; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D016899:Interferon-beta / Q000633:toxicity; D008727:Methotrexate / Q000633:toxicity; D051379:Mice; D008809:Mice, Inbred C3H; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D015376:Nimustine / Q000633:toxicity; D011994:Recombinant Proteins / Q000633:toxicity; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D015376:Nimustine; D016899:Interferon-beta; D004317:Doxorubicin; D008727:Methotrexate