Relationship between the Repair of Radiation-induced DMA Damage and Recovery from Potentially Lethal Damage in 9L Rat Brain Tumor Cells1

The kinetics of repair of radiation-induced DNA damage and recovery from radiation-induced potentially lethal damage (PLD) for fed plateau-phase 9L/Ro rat brain tumor cells were compared after single doses of 7-radiation and after combined treatment with 3 /tg of 1,3-bis(2-chloroethyl)-1 -nitrosourea (BCNU)/ml given 16 hr prior to irradiation. DNA damage and repair were assayed using alkaline filter elution, while cell survival was assayed by colony formation. Repair of radiation-induced DNA damage and recovery from radiation-induced PLD followed statistically iden tical biphasic kinetics; the fast-phase half-times were 4.1 ±0.3 (S.D.) min and 4.0 ±0.8 min, while the slow-phase half-times were 59.7 ±'\'\.2 min and 78.7 ±34.1 min, respectively. Treat ment with BCNU prior to irradiation resulted in both additional DNA damage and increased cell kill. When DNA damage and cell survival after the combined treatment were corrected for the contribution from BCNU given alone, no inhibition of either repair of radiation-induced DNA damage or of recovery from radiationinduced PLD was observed. However, postirradiation hypertonic treatment inhibited both DNA repair and recovery from radiationinduced PLD. These correlations between the kinetics of the molecular and cellular repair processes support a role for repair of radiation-induced DNA damage in recovery from radiationinduced PLD. The lack of inhibition by BCNU of both repair of radiation-induced DNA damage and of recovery from radiationinduced PLD also demonstrates that these are not the mecha nisms by which BCNU enhances radiation-induced cytotoxicity in 9L cells.