Endogenous N-nitrosation in man assessed by measurement of apparent total N-nitroso compounds in faeces

Abstract

The faecal concentration of substances responding to the chemical test for N-nitroso compounds (apparent total N-nitroso compounds, ATNC) was investigated in human subjects consuming their normal free-choice diet. Concentrations ranged from 40 to 590 micrograms (N-NO)/kg faeces. To ascertain the likely relative contributions of endogenous ATNC formation and preformed, dietary ATNC, the subjects consumed a diet low in nitrate and ATNC for 8 days. At the end of this period, ATNC had decreased substantially with concentrations ranging from below the 40 micrograms (N-NO)/kg detection limit up to 143 micrograms (N-NO)/kg, mean 82 micrograms (N-NO)/kg. On supplementing this diet with 300 mg nitrate/day, faecal ATNC levels increased markedly. On the third day of this regime, values were in the range 73-714 micrograms (N-NO)/kg with a mean of 307 micrograms (N-NO)/kg. The results, together with the known limited occurrence of ATNC in the majority of foodstuffs so far tested, generally non-detectable or less than 100 micrograms (N-NO)/kg, suggest that endogenous formation via species derived from dietary nitrate is likely to be an important source of ATNC in human faeces.

Hypermethylation of CpG island in O6-methylguanine-DNA methyltransferase gene was associated withK-rasG to A mutation in colorectal tumor

“…Alkylating agents causing the promutagenic lesion may be provided from dietary nitrates reduced in the proximal colon by bacteria, by nitrosation of amines and amides derived of protein catabolism [16,17] . During DNA replication, O 6 -methylguanine can pair with thymine, resulting in conversion of guanine-cytosine to adenine-thymine pairs in DNA [3] .…”

Generating mutations but providing chemosensitivity: the role of O6-methylguanine DNA methyltransferase in human cancer

“…For colorectal tumors, the alkylating agents causing the promutagenic lesion may be provided from dietary nitrates reduced in the proximal colon by bacteria, by nitrosation of amines and amides derived from protein catabolism (Ward et al, 1989;Bartsch et al, 1990;Rowland et al, 1991). For other cancers, these carcinogens are ever more speculative.…”

Dietary intake of different types and characteristics of processed meat which might be associated with cancer risk – results from the 24-hour diet recalls in the European Prospective Investigation into Cancer and Nutrition (EPIC)

“…Bingham et al 31 have shown that haem in red (fresh and processed) but not white meat substantially increases the endogenous burden of NOC. Excess nitrate can also increase endogenous NOC production 32 . The intake of the NOC precursor nitrite as well as the consumption of cured meat were positively associated with cancer risk of the prostate 10 and lower urinary tract 12 .…”