Fig. 1

Low doses of nitric oxide donors induce an antitumor response that is immune dependent. (A) Schematic of the tumor-bearing mouse model and the timeline of treatment with the nitric oxide donor S-nitroso-N-acetyl-DL-penicillamine (SNAP). LL2 tumor-bearing C57BL/6 mice received (B) 0.02, (C) 0.004, and (D) 0.0004 mg/kg SNAP. (E) B16F1 tumor-bearing C57BL/6 mice were administered 0.004 mg/kg SNAP by intraperitoneal injection. (F) LL2 tumor-bearing mice were administered SNP (0.1 mg/kg). (G) LL2 tumor-bearing C57BL/6 mice were administered 0.004 mg/kg isosorbide mononitrate (ISMN). (H) LL2 tumor-bearing immunodeficient NOD-SCID mice were administered 0.004 mg/kg SNAP or (I) 0.004 mg/kg ISMN by intraperitoneal injection. In all mice, 2 × 10⁵ Lewis lung carcinoma LL2 cells or B16F1 melanoma cells were implanted in the right flank. Tumor volumes were measured every 2-4 days beginning on the twelfth day after tumor implantation. The tumor results are presented as the means ± SEMs. *p < 0.05, **p < 0.01, ***p < 0.001. ns, no significant difference. All p-values were obtained by two-way ANOVA