THE EFFECT OF INTRASPINAL CYTOSINE-ARABINOSIDE ON THE REIRRADIATION 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 wi th 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 c ombined treatment may be impaired. In the present experiments immature , 3-week-old rats, were treated with ara-C and radiation on the cervic al spinal cord, and the long-term recovery was examined by reirradiati on after different intervals. The endpoint of the study was paresis du e to radiation myelopathy. The results showed a clear enhancement of t he radiation effect with a dose-modifying factor of 1.2, when ara-C wa s administered before irradiation. However, no indications for impaire d long-term recovery were observed. Additional experiments in adult ra ts with ara-C treatments during a 6-month interval between two radiati on doses also did not suggest any interference between ara-C treatment and long-term recovery of radiation induced injury. It is concluded t hat for both the adult and immature nervous tissue, only when ara-C is administered intraspinally shortly before irradiation, interaction be tween ara-C and radiation results in a significant reduction of the