Figure 1. Mechanistic models of nitric oxide (NO·)–mediated inhibition of tumorigenesis in p53-deficient mice.

A) NO·-mediated regulation of cellular proliferation and apoptosis in p53-deficient mice. Elevated levels of NO· production in p53-deficient mice with wild-type nitric oxide synthase 2 (NOS2) increase the expressions of the death receptor ligands, TRAIL and CD95-L (Fas-L), and the cell cycle checkpoint protein, p21waf1, to decrease tumorigenicity. B) Immune suppression model: The loss of NO·-related type 1 T-helper cell (TH1)–antitumor response and interleukin 10 (IL-10)–mediated inhibition of specific immune recognition and suppression of immune function can enhance tumorigenesis in mice deficient in both p53 and NOS2. Th2, type 2 T-helper cell; T-Reg, T-regulatory cells.