Hypoxia and reoxygenation in human melanoma xenografts

Tumor hypoxia and reoxygenation pattern following single dose (10.0 Gy) and fractionated (7 fractions of 2.0 Gy, 1 fraction per day) irradiation were studied in five human melanoma xenograft lines using the paired survival curve method. The hypoxic fractions differed significantly among the melanoma lines; they were found to be 6 +/- 3% (E.E.), 22 +/- 8% (E.F.), 31 +/- 11% (G.E.), 45 +/- 17% (M.F.), and 15 +/- 5% (V.N.). There were no clear correlations between hypoxic fraction and tumor volume-doubling time or vascular density, suggesting that intrinsic cellular characteristics, for example, rate of oxygen consumption and ability to retain clonogenicity under hypoxic stress, also may play an important role for the magnitude of the hypoxic fractions in the melanomas. Reoxygenation was rapid and extensive in all melanoma lines; 12-24 hr after the single dose irradiation or the last fraction of the fractionated irradiation, the hypoxic fractions were similar to those in untreated tumors and stayed at that level up to at least 10 days after irradiation. The hypoxic fractions 1-10 days after irradiation tended to be higher after fractionated than after single dose irradiation, but the differences were not statistically significant. There was a positive correlation between the hypoxic fractions in untreated tumors and the hypoxic fractions after irradiation and reoxygenation, suggesting that it may be possible to predict radiation resistance caused by hypoxia from the hypoxic fractions in tumors before start of radiation therapy. However, hypoxia is probably not a major cause of failure in the radiation therapy of malignant melanoma.