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The influence of methotrexate on radiation-induced damage to different lengths of the rat spinal cord

CRC Normal Tissue Radiobiology Research Group, Research Institute (University of Oxford), Churchill Hospital, Oxford OX3 7LJ, UK

An experimental model in the rat has been used to assess the possible enhancement of damage to the spinal cord when radiation is given in the presence of methotrexate (MTX). The dose of MTX used, 4 mg/kg, was the maximum dose that could be given to the rat, when administered into the cerebral spinal fluid circulation, without risk of serious neurological effects. Lengths of 4, 8 and 16 mm of the cervical spine were irradiated with single doses of X rays. For animals that developed paralysis within 30 weeks, caused predominantly by the presence of white matter necrosis, there was no evidence to indicate that MTX enhanced the radiation response of the rat spinal cord, at least at a more clinically relevant level of effect i.e. a low incidence of paralysis. However, for the doses associated with the 50% level of effect (ED₅₀) to an 8 mm long field a significant (p < 0.005) enhancement of the response was seen, suggesting a dose modification factor of 1.19 ± 0.07. This was interpreted in terms of an hypothesis to explain the well documented volume effect for very small fields in the rat spinal cord which is based on the migration of viable cells in the periphery of the irradiated site. The apparent smaller effect seen when only 4 mm of the spine was irradiated might be related to the nature of the lesion induced at doses required to produce paralysis in these small fields; the lesions were not restricted to white matter but were more severe and also involved the grey matter and nerve roots after a slightly shorter latent period.

Key Words: Rat spinal cord • Radiation myelopathy • Intrathecal methotrexate • Volume effect

Received for publication February 11, 1991. Revision received September 6, 1991. Accepted for publication September 20, 1991.