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A comparison of the effects of methotrexate and misonidazole on the germinal cells of the subependymal plate of the rat

CRC Normal Tissue Radiobiology Research Group, Research Institute (University of Oxford), The Churchill Hospital, Oxford, UK

The cytotoxic effects of the drugs methotrexate (MTX) and misonidazole have been assessed in the rat brain by quantifying changes in the constituent cell populations of a glial cell progenitor layer, the subependymal plate (SEP). Three distinct cell types can be identified in the SEP on the basis of their nuclear morphology: cells with small dark (SD), small light (SL) or large light (LL) nuclei. The cells with SD nuclei may represent pluripotential glial cell precursors. A reduction in the total nuclear density of the SEP, after the local ventricular administration of MTX, could be accounted for largely by a loss of cells with SD nuclei; to 45% of control values 2 days after MTX followed by a full recovery in numbers by day 5. A further decline in the number of cells with SD nuclei occurred at 12 weeks after MTX administration. The pattern of changes in the cellularity of the SEP, after misonidazole administration, were similar to those observed after MTX treatment, although the magnitude of the response was reduced. It was concluded that both drugs, but MTX in particular, could have a potential additive effect on glial progenitor cells when used in combination with other forms of cancer therapy including radiation.

Received for publication July 28, 1994. Revision received September 29, 1994. Accepted for publication November 17, 1994.

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