Electrochemistry and nitric oxide mass transport in cancer: why ingestion of sodium nitrite could be effective in treating vascularized tumors

Abstract

Nitric oxide concentrations in tumors do not reach apoptosis inducing levels when their excess NO is rapidly depleted. The out-flux of NO from a tumor to air or blood scales with the contacting area and with the concentration gradient; the gradient scales with the tumor–air or tumor–blood concentration difference and scales inversely with the thickness of the boundary layer, i.e. the fluid’s flow rate. Air-contacting skin and lung cancers account for ~60% of all cancers in part because out-diffusion of NO from nascent tumors to air increases the likelihood of their survival. Out-diffusion of NO also explains their initially 2-D spreading at the air interface. Blood is an NO sink because its proteins are rapidly S-nitrosated; depletion of NO by the blood explains the dormancy of tumors until their vascularization and their virulence after vascularization. Erythrocytes store NO₂- and their carbonic anhydrase converts it to NO and NO₃⁻. Thus, NaNO₂, a common additive in cured meats, may reduce NO out-diffusion by raising the blood NO concentration.