REIRRADIATION TOLERANCE OF RAT SPINAL-CORD TO FRACTIONATED X-RAY DOSES

Experiments were performed to assess the re-irradiation fractionation sensitivity in the rat cervical spinal cord. Animals were given initia lly three daily fractions of 9 Gy representing 75% of tolerance at the ED50 level. After an interval of 20 weeks, they were re-irradiated wi th graded doses of X-ray in single, 2, 5, 10 and 20 daily fractions, o r a single retreatment top-up dose of 12.8 Gy (equivalent to 80% of re treatment tolerance) followed by doses in 1, 2, 4, 1 0 and 20 daily fr actions. The end-point was paralysis of the forelimbs secondary to whi te matter necrosis. Latent periods to paralysis ranged from 188 to 245 days from initial irradiation, or from 48 to 105 days from re-irradia tion. For a given fractionated retreatment schedule, shorter latent ti mes were observed in animals re-irradiated to higher total doses. The re-irradiation ED50 values for single, 2, 5, 10 and 20 fractions were 14.0 (95% CI 13.3, 14.2), 20.5 (19.9, 21.2), 29.1 (28.0, 30.1), 36.3 ( 35.1, 37.4) and 47.8 Gy (46.2, 48.3), respectively. For re-irradiation s with a 12.8 Gy top-up dose followed by doses in single, 2, 4 and 20 fractions, the retreatment ED50 values excluding the 12.8 Gy top-up do se were 4.5 (95% CI 3.0, 5.4), 6.5 (5.6, 7.3), 7.0 (5.0, 8.1) and 10.9 Gy (8.9, 12.5), respectively. Direct fit of the linear-quadratic (LQ) model to the data gave similar alpha/beta values of 3.07 Gy (95% CI 2 .30, 3.95) and 3.34 Gy (95% CI 1.94, 4.74), respectively, p = 0.6, for the retreatment experiments without and with top-up doses. This fract ionation sensitivity during retreatment compares well with that of pre viously un-irradiated animals, alpha/beta value of 2.41 Gy for fractio n sizes down to 2 Gy/fraction. It is concluded that there is significa nt long-term recovery of radiation damage in rat spinal cord, and that previous radiation damage to a level of 75% of tolerance does not cha nge the capacity for repair of sublethal damage when the spinal cord i s re-irradiated with fractionated doses of X-ray at 20 weeks.