The effect of intraspinal cytosine arabinoside on the re-irradiation tolerance of the cervical spinal cord of young and adult rats.

Intrathecal treatment with cytosine arabinoside (ara-C) in combination with radiation has been used as prophylactic treatment in children with acute lymphatic leukaemia. Animal experiments have shown that ara-C enhances the effect of radiation on the spinal cord when administered shortly before irradiation, and that the long-term recovery after a combined treatment may be impaired. In the present experiments immature, 3-week-old rats, were treated with ara-C and radiation on the cervical spinal cord, and the long-term recovery was examined by reirradiation after different intervals. The endpoint of the study was paresis due to radiation myelopathy. The results showed a clear enhancement of the radiation effect with a dose-modifying factor of 1.2, when ara-C was administered before irradiation. However, no indications for impaired long-term recovery were observed. Additional experiments in adult rats with ara-C treatments during a 6-month interval between two radiation doses also did not suggest any interference between ara-C treatment and long-term recovery of radiation induced injury. It is concluded that for both the adult and immature nervous tissue, only when ara-C is administered intraspinally shortly before irradiation, interaction between ara-C and radiation results in a significant reduction of the isoeffective radiation dose by a factor of 1.2 (1.13-1.37, 95% confidence interval).