Tumor growth is significantly reduced in Gulo-/- mice on restricted ascorbic acid. Plasma ascorbic acid concentrations in Gulo-/- mice were measured before and at weekly intervals following depletion of ascorbic acid and during tumor growth for 6 weeks (n = 7 in all groups). (A) Lewis lung carcinoma cells were injected subcutaneously into Gulo-/- mice depleted of ascorbic acid for 4 weeks following which animals were either continued on a depleted diet (D) or a replete diet (D/R). A control group of Gulo-/- mice was fully supplemented with ascorbic acid before and after injection with Lewis lung carcinoma cells (R). Tumors were measured with microcalipers on indicated days (n = 10 per group). (B) Gulo-/- mice implanted with Lewis lung carcinoma cells were randomized to ascorbic acid depletion (D) or full repletion (R) when tumors were visible, and tumors were measured with microcalipers on indicated days (n = 10 per group). (C) Gulo-/- mice depleted of ascorbic acid were implanted with Lewis lung carcinoma cells and, when tumors were palpable, were randomized to depletion (D), 10% repletion (10%), or 100% (R) repletion, and tumors were followed for 10 days (n = 10 per group) (D).