ICRF-159 enhancement of radiation response in combined modality therapies. II. Differential responses of tumour and normal tissues.
The combined effect of the chemotherapeutic agent ICRF-159 and radiation on the proliferative status of tumor/normal systems has been evaluated using the Lewis lung tumour in BDF1 mice. We have previously shown that a 25 mg/kg dose of ICRF-159, given at 3h intervals X4 before irradiation, significantly enhanced tumour growth retardation relative to a single dose of 100 mg/kg before irradiation. Whilst both single and fractionated drug treatments produced a transient inhibition of cell proliferation, comparisons of the temporal recovery from the antiproliferative effect of radiation in both tumour and intestinal epithelium suggested that single acute doses of ICRF-159 fail to potentiate the radiation response of either tissue. Protracted drug administration before irradiation, however, markedly decreases the post-radiation proliferative recovery of the tumour, without significantly altering intestinal recovery. The data suggest that both drug concentration and/or exposure time determine the interactions seen with combined modes.
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D004334:Drug Administration Schedule; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D007583:Jejunum / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000628:therapy; D010879:Piperazines / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents; D011929:Razoxane / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D010879:Piperazines; D011838:Radiation-Sensitizing Agents; D011929:Razoxane