No abstract

High red meat diets have been linked with risk of sporadic colorectal cancer; but their effects on mutations which occur in this cancer are unknown. G-->A transitions in K-ras occur in colorectal cancer and are characteristic of the effects of alkylating agents such as N-nitroso compounds (NOC). We studied th effect of red meat consumption on faecal NOC levels in eight male volunteers who consumed diets low or high in meat (60 or 600 g/day), as beef, lamb or pork, whilst living in a metabolic suite. Increased intake of red meat induced a significant (P<0.024) 3-fold increase from 40 + or - 7 to ab average of 113 + or - 25 microgram/day NOC, a range of exposure in faeces similar to that from tobacco-specific NOC in cigarette smoke. THe diets were isoenergetic and contained equal amounts of fat, but concentrations of heterocyclic amines were low. Faecal excretion of the promotor ammonia was significantly increased to 6.5 + or - 1.08 mmol/day. When the high red meat diets were supplemented with 20 g phytate-free wheat bran in six volunteers there was no reduction in NOC levels (mean 138 + or - 41 microgram/day NOC), but faecal weight increased. Higher starch and non-starch polysaccharide intakes reduced intraluminal cross-linking in microcapsules (r=-0.77) and reduced faecal pH (r=-0.64). In two volunteers there was no effect of 600 g white meat and fish o faecal NOC (mean low white meat diet 68 + or - 10 microgram/day, high white meat 56 + or -6 microgram/day nor on faecal nitrate, nitrite and iron. Faecal nitrite levels increased on changing from a white to red meat diet (mean high white meat diet 46 + or - 7 mg/day, high red meat diet mean 80 + or - 7 mg/day.) Increased endogenous production of NOC and precursors from increased red meat, but not white meat and fish, consumption may be relevant to the aetiology of colorectal cancer.

No abstract

The heterocyclic aromatic amines (HAAs) 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) and 2-amino alpha carboline (A alpha C) were quantitated in grilled bacon and beef. The levels of PhIP in bacon ranged from < 0.1 to 52 p.p.b., MeIQx was detected at levels ranging from 0.9 to 18 p.p.b. Both 4,8-DiMeIQx and A alpha C were found at < 1 p.p.b. In grilled meat patties, MeIQx and PhIP were detected at levels ranging from 0.8 to 3.2 p.p.b., while 4,8-DiMeIQx and A alpha C were below the limit of detection (approximately 0.5 p.p.b.). HAAs were below the limit of detection in grilled fish. The bacon fat drippings and the pan scrapings obtained from grilled meat and fish also contained significant amounts of HAAs and indicated that either these carcinogens are released with the fat during grilling or that HAAs are formed directly in the released fat and juices. Several of these carcinogens were detected in the pan scrapings at concentrations 10- to 100-fold higher than in cooked meats. PhIP was detected at 144 p.p.b. in combined grilled meat and fish scrapings, followed by A alpha C at 77 p.p.b., MeIQx at 29 p.p.b. and 4,8-DiMeIQx at 4 p.p.b. The co-mutagens harman and norharman were also detected in cooked meats and fish at amounts ranging from 5 to 30 p.p.b. Fat drippings and grill residue scrapings are often used as a base for gravies and sauces. Thus, cooking practices and dietary habits have a strong impact on HAA exposure.

Two solid-phase extraction methods were developed for the determination of mutagenic heterocyclic aromatic amines in heated meat products. The copper phthalocyanine (CPC) tandem extraction was performed on coupled cartridges of diatomaceous earth and CPC-derivatized Sephasorb HP, followed by further clean-up on Sephasorb HP. Parts per billion levels of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and its homologs as well as 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), amino-alpha-carboline (A alpha C), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), harman (H) and norharman (NH) can then be simultaneously quantified by HPLC with UV detection. The propylsulfonyl silica gel (PRS) tandem extraction is a one-step clean-up method on coupled cartridges of diatomaceous earth and PRS, suitable for the determination of MeIQx, IQ and their homologs, as well as the glutamic acid pyrolysates 2-amino-6-methyldipyrido[1,2-a:3',2']imidazole (Glu-P-1) and 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2). 4,7,8-TriMeIQx or 7,8-DiMeIQx were used as internal standards. Four grams of sample or less are required for analysis. The recovery of the amines was between 46 and 83% and the detection limit was in the low p.p.b. range with coefficients of variation ranging between 5 and 18%. The major mutagenic contaminant found in meat extracts was MeIQx (from less than 1 to 44 p.p.b.), followed by 4,8-DiMeIQx (1.3-5 p.p.b.) whereas the major contaminant in fried meat was PhIP (23-48 p.p.b.), followed by MeIQx (5.1-8.3 p.p.b.), A alpha C (3.2-8.9 p.p.b.) and 4,8-DiMeIQx (1.3-2 p.p.b.). The co-mutagens NH and H were found in fried meat at levels of 8.7-19 p.p.b. and 3-4.8 p.p.b. respectively.