Modification of radiation damage in rat spinal cord by mitotane

Modification of the paralytic response in rats after 6-MV photon irradiation of the spinal cord with either single or split exposures (two equal fractions given in a 24-hour period) by mitotane was investigated. Mitotane was administered as a suspension in physiologic saline (300 mg/kg/day) for either 5 days prior to or 5 days after irradiation. For rats receiving split doses of 6-MV photons, either the last two doses of mitotane were given 2 hours prior to each radiation fraction or mitotane was begun 2 hours after the second fraction and continued for 5 days. The data to 6 months after irradiation indicate that, in rats given mitotane for 5 days prior to single-dose photon irradiation, the paralytic response (as defined by the dose needed to produce paralysis in 50% of the irradiated groups of rats) was enhanced by a dose-enhancement factor (DEF) of 1.40. The DEF in the group of rats given mitotane after single doses of 6-MV photons was 1.15. In the split-dose irradiation experiments, the DEF for the groups of rats given mitotane prior to each radiation fraction was 1.36; while the DEF for the group of rats receiving mitotane beginning after the second fraction was 1.18. These data indicate that mitotane can potentiate the effects of 6-MV photon irradiation to the central nervous system, with mitotane administered prior to irradiation being the most effective sequence.