Stuart Shephard

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A literature review has shown that the daily intakes of various N-nitroso-precursor classes in a typical European diet span five orders of magnitude. Amides in the form of protein, and guanidines in the form of creatine and creatinine, are the nitrosatable groups found most abundantly in the diet, approaching levels of 100 g/day and 1 g/day, respectively.(More)
In a commentary in Vol. 20. No. 3, ofthis joumal, Ashby and Lcigibcl [ 19921 warned of possible confusion in the understanding of gcnotoxic and nongenotoxic carcinogens becausc thc ncw transgenic mutation assays might open thc possihility of dctecting mutagenic activitics of chemieals unrclated to their presence in the cell at the momcnt of mutation(More)
Naturally occurring dipeptides, cholecystokinine (CCK, a tetrapeptide hormone) and the artificial sweetener aspartame were nitrosated for 10-30 min with 40 mM-nitrite (pH 3.5, 37 degrees C), and the resultant products examined for mutagenicity in Salmonella typhimurium TA100. Specific mutagenicities (net revertants per mumol precursor) spanned four orders(More)
Nitrosation of dietary components has been combined with the 4-(para-nitrobenzyl)pyridine (NBP) colorimetric test for screening alkylating agents and with the Ames test for the detection of mutagenic activity. This allowed the investigation of short-lived nitrosation products of dietary components which generate electrophilic degradation products requiring(More)
The diet contains a large number of constituents which can be nitrosated in the gastrointestinal tract (especially in the stomach) to potentially carcinogenic nitroso compounds (NOC). The nitrosation of food mixtures has been investigated with a number of assays, such as chemical analysis or detection of alkylating potential, mutagenicity and(More)
2-Acetylaminofluorene (2-AAF) was administered at levels of 0, 300 and 600 ppm in the diet for 28 days to female transgenic mice bearing the lacI gene in a lambda vector (Big Blue mice). The lambda vector was excised from liver DNA and packaged in vitro into bacteriophage particles which were allowed to infect E. coli bacteria, forming plaques on agar(More)
The mutagenic potency of the common mushroom Agaricus bisporus and crude agaritine extracted from mushrooms was determined in vivo using a new mutagenesis assay with lacI transgenic mice (Big Blue mice). Pairs of female lacI mice were fed one of three diets for 15 wk: (1) fresh mushrooms 3 days/wk followed by normal lab chow for 4 days/wk; (2) freeze-dried(More)
The detection limit of the lacI transgenic mouse mutagenicity assay lies, in practice, at approximately a 50-100% increase in mutant frequency in treated animals over controls. The sensitivity of this assay in detecting genotoxins can be markedly improved by subchronic rather than acute application of the test compound. The lacI transgenic mouse(More)
The potential health risk posed by the endogenous formation of N-nitroso compounds (NOC) from nitrosation of dietary ureas, guanidines, amides, amino acids and amines (primary, secondary and aromatic) was estimated according to the model: Risk = [daily intake of precursor] X [gastric concentration of nitrite]n X [nitrosatability rate constant] X(More)
In a colorimetric assay using 4-(p-nitrobenzyl)pyridine (NBP) as a nucleophilic scavenger of alkylating agents, the nitrosation and alkylation reactions were investigated for a number of amino acids and derivatives. The alkylating activity increased with the square of the nitrite concentration. The nitrosation rate constants for aspartic acid, aspartame,(More)