Figure 4.

The capacity for net acid extrusion is increased in both normal breast tissue and breast cancer tissue from NaHCO₃-treated mice compared to control mice. (A, B). Average traces of pH_i-dynamics during NH₄⁺-prepulse experiments performed on normal breast tissue (A) and breast cancer tissue (B) from NaHCO₃-treated mice and control mice (n = 7). Experiments were conducted in both the presence and absence of CO₂/HCO₃^–. (C). Intracellular intrinsic buffering capacity of organoids of both cancer and normal tissue from NaHCO₃-treated and untreated mice (n = 7). Linear regression showed no significant difference in buffering capacity between NaHCO₃-treated and control mice. (D,E). Cellular net acid extrusion in epithelial organoids isolated from normal breast tissue (D) and breast cancer tissue (E) displayed as a function of pH_i. Experiments were based on tissue from NaHCO₃-treated mice and control mice (n = 7) and performed in both the presence and absence of CO₂/HCO₃^–. Data were compared by least-squares linear regression analyses. (F). Breast tumor-free survival plotted as function of net acid extrusion capacity displayed as the pH_i value corresponding to net acid extrusion of 14 mM/min. The higher the pH_i value, the greater the capacity for net acid extrusion. (G,H). Steady-state pH_i values measured from normal breast tissue (G) and breast cancer tissue (H) isolated from NaHCO₃-treated mice and control mice (n = 7) and investigated at pH_o 7.4 (closed symbols) and 6.8 (open symbols). Data were compared by three-way ANOVA. *p < 0.05, **p < 0.01, ***p < 0.001 vs. Control under similar conditions or as indicated.