Experimental studies on interactions of radiation and cancer chemotherapeutic drugs in normal tissues and a solid tumour.

The interactions of radiation and seven cancer chemotherapeutic drugs have been investigated in four normal tissues (intestinal crypts, skin, haemopoietic tissue and lung) and in a solid C3H mouse mammary carcinoma in vivo. All experiments were carried out with male C3D2F1 mice. 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). Single drug doses were given at different intervals before, simultaneously with and after single doses of radiation. The normal tissue reactions following drug-radiation combinations were found to be highly complex. The interactions varied both quantitatively and qualitatively from drug to drug and from tissue to tissue. The drugs enhanced the radiation response in most cases. However, signs of radioprotection was observed for CTX in skin and for MTX in haemopoietic tissue. The interval and the sequence of the two treatment modalities were of utmost importance for the normal tissue reactions. In general, the most serious interactions occurred when drugs were administered simultaneously with or a few hours before radiation. The radiation-modifying effect of the drugs deviated from this pattern in the haemopoietic tissue as the radiation response was most enhanced on drug administration 1-3 days after radiation. Enhancement of the radiation response was generally less pronounced in the tumour model than in the normal tissues. The combined drug-radiation effect was apparently less time-dependent in the tumour than in the normal tissues.