Tumor-dependent kinetics of partial pressure of oxygen fluctuations during air and oxygen breathing

The primary purpose of this study was to examine the kinetics of partial pressure of oxygen (pO₂) fluctuations in fibrosarcoma (FSA) and 9L tumors under air and O₂ breathing conditions. The overall hypothesis was that key factors relating to oxygen tension fluctuations would vary between the two tumor types and as a function of the oxygen content of the breathing gas. To assist in the interpretation of the temporal data, spatial pO ₂ distributions were measured in 10 FSA and 8 9L tumors transplanted into the subcutis of the hind leg of Nembutal-anesthetized (50 mg/kg) Fischer 344 rats. Recessed-tip oxygen microelectrodes were inserted into the tumor, and linear PO₂ measurements were recorded in 50-μm steps along a 3-mm path, and blood pressure was simultaneously measured via femoral arterial access. Additionally, PO₂ was measured at a single location for 90 to 120 minutes in FSA (n = 11) or 9L tumors (n = 12). Rats were switched from air to 100% O₂ breathing after 45 minutes. Temporal pO₂ records were evaluated for their potential radiobiological significance by assessing the number of times they crossed a 10-mm-Hg threshold. In addition, the data were subjected to Fourier analysis for air and O₂ breathing. FSA and 9L tumors had spatial median PO₂ measurements of 4 and 1 mm Hg, respectively. 9L had more low pO₂ measurements ≤2.5 mm Hg than did FSA, whereas between 2.5 and 10 mm Hg this pattern was reversed. Pimonidazole staining patterns in FSA and 9L tumors supported these results. Temporal pO₂ instability was observed in all experiments during air and O₂ breathing. Threshold analyses indicated that the 10 mm Hg threshold was crossed 2 to 5 times per hour, independent of tumor type. However, the magnitude of 9L pO₂ fluctuations was approximately eight times greater than FSA fluctuations, as assessed with Fourier transform analysis (Wilcoxon, P < 0.005). O₂ breathing significantly increased median pO₂ in FSA from 3 to 8 mm Hg (P < 0.005) and caused a significant increase in frequency and magnitude of pO₂ fluctuations. One hundred percent O₂ breathing had no effect on 9L tumor pO₂, and it decreased the magnitude of pO₂ fluctuations with borderline significance. These results show that these two tumors differ significantly with respect to spatial and temporal oxygenation conditions under air and O ₂ breathing. Fluctuations of pO₂ of the type reported herein are predicted to significantly affect radiotherapy response and could be a source for genetic instability, increased angiogenesis, and metastases.