The longterm objectives of this radiobiological study are centered upon finding commbinations of radiation with cytotoxic drugs whose effects are superior to those of the constituent modalities alone or of their algebraic sums. The 5 specific aims are: to investigate the generality of the supraadditive effect produced when cis-Pt is added to fractionated radiation (5 daily doses); to investigate the mechanism of this supra-additive response; to investigate whether supra-additive responses occur also in important normal tissues and thus to derive therapeutic gain factors; to investigate whether tumor response is improved using cytotoxic drugs (notably but not exclusively cis-Pt) combined with fractionated radiation schedules other than 5 daily doses; to determine whether supra-additivity is related to the productive recruitment of non-cycling tumor cells (RIF-1 and EMT6 tumors); and if this is the case, to determine the optimum times for treatment with different modalities. All experiments will be done in mice (C3H/Km or BALB/c/Ka) either on syngeneic tumors (RIF-1, EMT6, KHT, or SCC VII/St) or on normal tissues. Tumor response will assessed by regrowth delay, TCD50, or in vivo/in vitro excision assay. Q cell recruitment will be studied by the labeled microcolony method using SACCAS to analyze autoradiographs. Normal tissues and endpoints include spinal cord/myelitis, lung/LD50/160 days, kidney/LD50 2.5 mos. after unilateral nephrectomy, duodenum and colon/crypt survival, and acute macroscopically visible response of the skin. The results of this project should be applicable to human cancer therapy. Disciplines most directly involved: radiobiology, radiation therapy and medical oncology.
