Chonnam Med J.  2002 Mar;38(1):24-29.

In vitro Model to Assess Neurotoxicity Induced by Anticancer Chemotherapeutic Agents

• Cho KH
• Kim JK

Abstract

Most chemotherapeutic agents have some deleterious side effect on normal host tissues. Also 5-Fluorouracil (5-FU), a common anticancer drug, carries a risk of central nervous system toxicity such as leukoence-phalopathy. We examined the ability of 5-FU exposure to kill cultured mouse cortical neurons and glia. Mixed neuron/glial, astrocytic, and mixed oligodendrocyte/astrocyte cultures were exposed to 5-FU for 24 hours. Neuron and astrocyte damage was assessed by LDH assay and oligodendrocyte death was assessed by counting the number of viable galactocerebroside positive (Gal-C(+)) cells per 100 x field. Neurons and astrocytes exposed to 10, 30, 100 and 300 micro M 5-FU produced no changes in morphology and level of LDH. But mixed oligodendrocyte/astrocyte cultures exposed to 10, 30, and 100 micro M 5-FU developed concentration-dependent oligodendrocyte death. Most oligodendrocytes were damaged by 100 micro M 5-FU, but there was little damage on astrocytes. These findings suggest that oligodendrocytes are selectively vulnerable to 5-FU, and neurons and astrocytes were relatively resistant to 5-FU. Present observations raise the possibility that leukoencephalopathy associated with 5-FU may be caused by the drug induced death of oligodendrocyte.

Keyword

5 Fluorouracil; Leukoencephalopathy; Oligodendrocyte

MeSH Terms

Animals
Astrocytes
Central Nervous System
Fluorouracil
Leukoencephalopathies
Mice
Neuroglia
Neurons
Oligodendroglia
Fluorouracil