FRACTION OF RADIOBIOLOGICALLY HYPOXIC CELLS IN HUMAN-MELANOMA XENOGRAFTS MEASURED BY USING SINGLE-CELL SURVIVAL, TUMOR-GROWTH DELAY AND LOCAL TUMOR-CONTROL AS END-POINTS

Four human melanoma xenograft lines (A-07, D-12, R-18, U-25) grown ort hotopically in Balb/c nu/nu mice were characterized with respect to th e fraction of radiobiologically hypoxic cells, The purpose of the stud y was to establish a firm radiobiological basis for future use of the lines in the development and evaluation of non-invasive assays of tumo ur hypoxia. The hypoxic fractions were assessed using three different assays, the single cell survival assay, the tumour growth delay assay and the local tumour control assay, and the means +/- s.e. were found to be 6 +/- 3%, 3 +/- 1% and 5 +/- 2% respectively (A-07), 26 +/- 5%, 25 +/- 6% and 22 +/- 6% respectively (D-12), 55 +/- 9%, 65 +/- 8% and 48 +/- 7% respectively (R-18) and 52 +/- 8%, 59 +/- 7% and 47 +/- 7% r espectively (U-25). The three assays gave numerical values for the hyp oxic fraction that were not significantly different for any of the lin es. The hypoxic fraction differed significantly among the lines; the R -18 and U-25 lines showed higher hypoxic fractions than the D-12 line (P < 0.05), which in turn showed a higher hypoxic fraction than the A- 07 line (P < 0.05), regardless of the assay. The wide range of the hyp oxic fractions and the significant differences among the lines suggest that A-07, D-12, R-18 and U-25 tumours should be useful models in fut ure studies attempting to develop non-invasive assays of tumour hypoxi a.