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.

Consumption of fruits and vegetables has been associated with a decrease in cancer incidence and cardiovascular disease, presumably caused by antioxidants. We designed a human intervention study to assess antioxidative and possible anti-genotoxic properties of fruit-borne antioxidants. We hypothesized that individuals bearing genetic polymorphisms for genes related to quercetin metabolism, benzo[a]pyrene metabolism, oxidative stress and DNA repair differ in their response to DNA protective effects of increased antioxidant intake. In the present study, 168 healthy volunteers consumed a blueberry/apple juice that provided 97 mg quercetin and 16 mg ascorbic acid a day. After a 4-week intervention period, plasma concentrations of quercetin and ascorbic acid and trolox equivalent antioxidant capacity (TEAC) were significantly increased. Further, we found 20% protection (P < 0.01) against ex vivo H(2)O(2)-provoked oxidative DNA damage, measured by comet assay. However, the level of ex vivo induced benzo[a]pyrene-diol-epoxide (BPDE)-DNA adducts was 28% increased upon intervention (P < 0.01). Statistical analysis of 34 biologically relevant genetic polymorphisms revealed that six significantly influenced the outcome of the intervention. Lymphocytes from individuals bearing variant genotype for Cyp1B1 5 seemed to benefit more than wild-types from DNA damage-protecting effects upon intervention. Variants for COMT tended to benefit less or even experienced detrimental effects from intervention. With respect to GSTT1, the effect is ambiguous; variants respond better in terms of intervention-related increase in TEAC, but wild-types benefit more from its protecting effects against oxidative DNA damage. We conclude that genotyping for relevant polymorphisms enables selecting subgroups among the general population that benefit more of DNA damage-modulating effects of micronutrients.

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Placental TL decreases during the third trimester of gestation of live-born twins with approximately 25% indicating that telomere shortening may play a role in aging of the placenta.

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