REDUCTION OF HYPOXIC CELLS IN SOLID TUMORS INDUCED BY MILD HYPERTHERMIA - SPECIAL REFERENCE TO DIFFERENCES IN CHANGES IN THE HYPOXIC FRACTION BETWEEN TOTAL AND QUIESCENT CELL-POPULATIONS

C3H/He mice bearing SCC VII tumours received 5-bromo-2'-deoxyuridine ( BrdU) continuously for 5 days via implanted miniosmotic pumps in order to label all proliferating (P) cells. The tumours were then heated at 40 degrees C for 60 min. At various time points after heating, tumour -bearing mice were irradiated while alive or after being killed. Immed iately after irradiation, the tumours were excised, minced and trypsin ized. The tumour cell suspensions obtained were incubated with cytocha lasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency i n cells without BrdU labelling, which could be regarded as quiescent ( Q) cells, was determined using immunofluorescence staining for BrdU. T he MN frequency in the total (P+Q) tumour cell population was determin ed from the irradiated tumours that were not pretreated with BrdU. The MN frequency of BrdU unlabelled cells was then used to calculate the surviving fraction of the unlabelled cells from the regression line fo r the relationship between the MN frequency and the surviving fraction of total (P+Q) tumour cells. In general, Q cells contained a greater hypoxic fraction (HF) than the total tumour cell population. Mild heat ing decreased the HF of Q cells more markedly than in the total cell p opulation, and the minimum values of HFs of both total and Q cell popu lations were obtained 6 h after heating. Two days after heating, the H F of total tumour cells returned to almost that of unheated tumours. I n contrast, the HF of Q cells did not return to the HF level of unheat ed tumours until 1 week after heating. It was thought that irradiation within 12 h after mild heating might be a potentially promising thera peutic modality for controlling radioresistant Q tumour cells.