Figure 7. Models Illustrating the Linkage Between DNA Damage, the NHE-1 Antiport, Alkalinisation, Bcl-x_L Deamidation, and Apoptosis in Wild-Type and Cancer Cells.

(A) In wild-type thymocytes, DNA damage causes increased NHE-1 expression and a consequent rise in intracellular pH, Bcl-x_L deamidation, and apoptosis.

(B) In pretumourigenic thymocytes expressing an OTK, the DNA damage–induced rise in NHE-1 expression is blocked, preventing alkalinisation, Bcl-x_L deamidation, and apoptosis.

(C) Enforced alkalinisation of murine tumour cells, or human B-CLL cells, causes Bcl-x_L deamidation and subsequent apoptosis, even in the absence of external genotoxic attack.