Endogenous N-Nitroso Compounds, and Their Precursors, Present in Bacon, Do Not Initiate or Promote Aberrant Crypt Foci in the Colon of Rats

Abstract

Processed meat intake is associated with increased risk of colorectal cancer. This association may be explained by the endogenous formation of N-nitroso compounds (NOC). The hypothesis that meat intake can increase fecal NOC levels and colon carcinogenesis was tested in 175 Fischer 344 rats. Initiation was assessed by the number of aberrant crypt foci (ACF) in the colon of rats 45 days after the start of a high-fat bacon-based diet. Promotion was assessed by the multiplicity of ACF (crypts per ACF) in rats given experimental diets for 100 days starting 7 days after an azoxymethane injection. Three promotion studies were done, each in 5 groups of 10 rats, whose diets contained 7%, 14%, or 28% fat. Tested meats were bacon, pork, chicken, and beef. Fecal and dietary NOC were assayed by thermal energy analysis. Results show that feces from rats fed bacon-based diets contained 10-20 times more NOC than feces from control rats fed a casein-based diet (all p < 0.0001 in 4 studies). In bacon-fed rats, the amount of NOC input (diet) and output (feces) was similar. Rats fed a diet based on beef, pork, or chicken meat had less fecal NOC than controls (most p < 0.01). No ACF were detected in the colon of bacon-fed uninitiated rats. After azoxymethane injection, unprocessed but cooked meat-based diets did not change the number of ACF or the ACF multiplicity compared with control rats. In contrast, the bacon-based diet consistently reduced the number of large ACF per rat and the ACF multiplicity in the three promotion studies by 12%, 17%, and 20% (all p < 0.01). Results suggest that NOC from dietary bacon would not enhance colon carcinogenesis in rats.

Meat Processing and Colon Carcinogenesis: Cooked, Nitrite-Treated, and Oxidized High-Heme Cured Meat Promotes Mucin-Depleted Foci in Rats

“…2). Fecal ATNC may not promote ACF formation (11,52) but may explain the MDF promotion observed here.…”

“…Nitrites are nitrosating agents and can interact with secondary amino compounds to form N-nitroso compounds. Parnaud et al (11,52) showed that rats fed fried bacon excrete 10 to 20 times more ATNC in feces than controls, but these ATNC do not initiate ACF in rats, nor do they promote ACF in azoxymethane-initiated rats. Haorah et al (53) showed that hotdogs contain 10 times more ATNC than fresh red meat.…”

“…Red meat enhances the formation of putative carcinogenic N-nitroso compounds in human feces (8)(9)(10). But N-nitroso compounds brought into the rat intestine by a bacon-based diet did not initiate nor promote preneoplastic lesions in rat colon (11). Meat cooked at a high temperature contains mutagenic heterocyclic aromatic amines that induce colon, mammary, and prostate tumors in rodents and monkeys (12).…”

Mechanisms Linking Colorectal Cancer to the Consumption of (Processed) Red Meat: A Review

“…They demonstrated a dose-response increase in fecal excretion of NOCs with red meat intake, not observed with vegetable proteins, white meat or an Fe CC supplement, but clearly mimicked by a heme supplement. Also in animal studies, inclusion of red or processed red meat into the diet increased the fecal concentration of NOCs (Parnaud et al, 2000;Mirvish et al, 2003). However, the analytical method used to analyze NOCs did not differentiate between N-nitrosamines and other compounds such as Snitrosothiols, O-nitroso compounds and nitrosyl iron.…”

Nitric Oxide Synthase and Nitric Oxide Involvement in Different Toxicities

“…− is the precursor of N-nitroso compounds that have carcinogenic effect [58,59]. NO 2 − is converted into nitrous acid in acidic environment, and nitrous acids react with secondary amines to form nitrosamine compounds (Figure 2) [60].…”