Volatile N-nitrosamine formation after intake of nitrate at the ADI level in combination with an amine-rich diet.

Abstract

Formation of nitrite from ingested nitrate can result in several adverse health effects and implies a genotoxic risk as a consequence of endogenous formation of carcinogenic N-nitroso compounds. We studied the formation of volatile N-nitrosamines after intake of nitrate at the acceptable daily intake (ADI) level in combination with a fish meal rich in amines as nitrosatable precursors. Twenty-five volunteers consumed this meal during 7 consecutive days; a diet low in nitrate was consumed during 1 week before and 1 week after the test week. Nitrate intake at the ADI level resulted in a significant rise in mean salivary nitrate and nitrite concentrations. Mean urinary nitrate excretion increased from 76 mg/24 hr in the first control week to 194 and 165 mg/24 hr in the test week, followed by a decline to 77 mg/24 hr in the second control week. The urine samples were analyzed for volatile N-nitrosamines, and both N-nitrosodimethylamine (NDMA) and N-nitrosopiperidine (NPIP) were detected in the samples. Mean urinary NDMA excretion significantly increased from 287 ng/24 hr in the control week to 871 and 640 ng/24 hr in the test week and declined to 383 ng/24 hr in the second control week. Excretion of NPIP was not directly related to the nitrate intake and composition of the diet. Nitrate excretion and NDMA excretion were significantly correlated, as well as salivary nitrate and nitrite concentration and NDMA excretion. We conclude that nitrate intake at the ADI level in combination with a fish meal containing nitrosatable precursors increases NDMA excretion in urine and thus demonstrates increased formation of carcinogenic N-nitrosamines.

Identification of Adducts Formed in the Reaction of α-Acetoxy-N-nitrosopyrrolidine with Deoxyribonucleosides and DNA

“…Adducts 13, 16 and 17 were directly identified by the spectral data described below. Similarly, Figure 1C shows a peak corresponding to (M + H) + of dThd adduct(s) (18,19, and/or 20), which also disappeared upon NTH ( Figure 1G). We could not obtain NMR data on this dThd adduct(s).…”

0908 The role of red and processed meat in colorectal cancer development: A perspective

“…NOC can be found in normal human feces, urine and saliva, and it has been suggested that this is due to in vivo nitrosation of ingested secondary and tertiary amines (Kakizoe et al, 1979). This process may be further catalyzed by the presence of heme iron, which is also present in processed meat (Cross, Pollock, & Bingham, 2003;Vermeer, Pachen, Dallinga, Kleinjans, & van Maanen, 1998). Recently, human studies have demonstrated that indeed under normal dietary conditions urinary markers of exposure to N-nitroso compounds are associated with micronucleus frequencies, a validated marker of carcinogenic risk, as well as with gene expression changes that are involved in cancer development (Hebels, Jennen, et al, 2011).…”

Nitrate Accumulation and Vegetable Quality

“…Epidemiological studies have not provided any evidence that there is an increased risk of cancer related to high nitrate intake from sources other than vegetables. In some cases studies revealed a negative correlation between nitrate intake and gastric cancer (Beresford, 1985) because vegetables are an excellent source of vitamins, minerals and biologically active compounds (Vermeer et al, 1998).…”