Interactions of Drugs and Radiation in Haemopoietic Tissue Assessed by Lethality of Mice after Whole-body Irradiation

Summary

Drug-radiation interactions in haemopoietic tissue were assessed as the lethality of mice within 7–28 days after whole-body irradiation. The investigated drugs were adriamycin (ADM), bleomycin (BLM), cyclophosphamide (CTX), 5-fluorouracil (5-FU), methotrexate (MTX), mitomycin C (MM-C) and cis-diamminedichloroplatinum II (cis-DDP). The drugs were administered as single doses 15 min before graded doses of whole-body irradiation or at different intervals from 7 days before to 7 days after fixed radiation doses. ADM, CTX, 5-FU, MM-C and cis-DDP enhanced the radiation response when administered 15 min before irradiation. The dose effect factor (DEF) was 9·11 for 5-FU and in the range 1·25–1·59 for the other drugs. MTX administration 15 min before irradiation had no effect (DEF 1·00). However, MTX increased lethality if given 1–3 days after irradiation (DEF 1·21–1·76) and protected against lethality if given 1–3 days before irradiation (DEF 0·83). A similar time dependence was observed for ADM, CTX, 5-FU, MM-C and cis-DDP. Protection against lethality was not observed but in all these cases the lethality was significantly lower at administration 1–3 days before than 1–3 days after irradiation. A proper investigation of the effect of BLM was not possible as the combination of this drug and whole-body irradiation caused a high rate of gastrointestinal deaths.

• haemopoietic tissue
• whole-body irradiation
• drugs
• drug-radiation interactions