Tumor-line specific pO2 fluctuations in human melanoma xenografts

Purpose: A large number of studies have demonstrated that tumors are heterogeneous in oxygen tension (pO(2)) and may develop regions with chronically or acutely hypoxic cells during growth. In the present study, it was investigated whether experimental tumors of different lines may sh<ow characteristic pO(2) fluctuation patterns and hence may differ with respect to the kinetics of acute hypoxia. Methods and Materials: A total of 70 xenografted tumors of two human melanoma lines (A-07 and R-18) were included in the study. Tissue pO(2), was measured simultaneously in two positions in each tumor for periods of at least 60 min using a two-channel fiberoptic oxygen-sensing device (OxyLite 2000, Oxford Optronix, Oxford, UK). Results: The mean pO(2), was calculated for each pO(2) trace, and this parameter was significantly greater in A-07 than in R-18 tumors (p <0.000001). Fluctuations in pO(2), around 3, 5, or 10 mm Hg were seen in a large fraction of the tumors of both lines. The pO(2) fluctuation frequency differed among individual traces from 0 to 20/h (A-07) and from 0 to 12/h (R-18) and was significantly greater in A-07 than in R-18 tumors (p = 0.0026). The absolute amplitude of the pO(2) fluctuations ranged from 1 to 16 mm Hg (A-07) and I to 33 rum Hg (R-18) and did not differ between the tumor lines. The relative amplitude was significantly higher in R-18 than in A-07 tumors (p 0.000001). The pO(2) values recorded simultaneously in the same tumor were in general not temporally coordinated. Conclusion: Experimental tumors of different lines may show individual and characteristic pO(2), fluctuation patterns. The pO(2) fluctuations may result in regions with acutely hypoxic cells. The kinetics of the acute hypoxia may differ among tumors of different lines, individual tumors of the same line, and different regions within the same tumor. (C) 2004 Elsevier Inc.