Effects of intrathecal methotrexate and cytosine arabinoside on the radiation tolerance of the rat spinal cord.

The effect of intrathecally or intravenously administered methotrexate (MTX) or cytosine arabinoside (ara-C) on the early and late delayed radiation response of the rat cervical spinal cord has been studied. A technique has been developed for intrathecal administration of drugs into the rat lumbar spinal canal. When given shortly before irradiation, intrathecal ara-C significantly reduces the isoeffect doses for the early delayed white matter necrosis syndrome by a factor of 1.2-1.3, while no effect is observed for the late delayed vascular syndrome. The effect disappears when ara-C is given intravenously or 24 h after irradiation. In addition, intrathecal ara-C seems to impair the capacity of long-term regeneration. Intrathecal administration of MTX is limited by severe acute neurotoxicity. At a maximally tolerated intrathecal MTX dose, no modification of the early or late radiation response of the spinal cord was observed. In contrast to ara-C, intravenous MTX seems to interact with the induction of the late delayed vascular damage in the rat cervical spinal cord, with a dose-modifying factor of 1.1-1.2.