Studies on in vivo Formation of Nitroso Compounds

The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway

“…Salivary nitrate levels at baseline are .10-fold higher than circulating plasma nitrate levels (Spiegelhalder et al, 1976;Lundberg and Govoni, 2004), indicating a concentration of nitrate within the oral cavity. This circuit of nitrate is a relatively quick process; within 20-60 minutes post-inorganic nitrate load, an elevation in salivary nitrate levels is detectable (Harada et al, 1974;Ishiwata, 1976b;McKnight et al, 1997).…”

“…These early studies demonstrated that in addition to these rises in salivary nitrate with oral nitrate dosing, rises in the chemically related but distinct anion nitrite occur hand in hand. It is noteworthy that the primary aim of these investigations was to determine whether nitrate ingestion might result in sufficient nitrite generation to lead to formation of N-nitroso compounds linked to carcinogenesis (Harada et al, 1974;Tannenbaum et al, 1974Tannenbaum et al, , 1976Eisenbrand et al, 1980). Studies have shown that there is no nitrite in saliva taken directly from salivary gland ducts, as opposed to mixed saliva in the oral cavity, indicating that conversion of nitrate to nitrite within the oral cavity, and not within the salivary glands, was responsible for salivary nitrite levels.…”

“…The potential for carcinogenesis has long been a concern in relation to nitrite and nitrate biology. Indeed, almost all of the works in the 1970s and 1980s looking at oral nitrate reduction were done for the purpose of exploring possible contributions to carcinogenesis via N-nitrosamines (Harada et al, 1974;Tannenbaum et al, 1974Tannenbaum et al, , 1976Ishiwata et al, 1975a,b,c,d;Ishiwata, 1976a,b;Spiegelhalder et al, 1976;Eisenbrand et al, 1980;Tannenbaum and Correa, 1985), and more recently, concerns have been re-expressed relating to cancers in the upper GI tract (Iijima et al, 2003).…”