Meat processing and colon carcinogenesis: cooked, nitrite-treated, and oxidized high-heme cured meat promotes mucin-depleted foci in rats

Abstract

Processed meat intake is associated with colorectal cancer risk, but no experimental study supports the epidemiologic evidence. To study the effect of meat processing on carcinogenesis promotion, we first did a 14-day study with 16 models of cured meat. Studied factors, in a 2 x 2 x 2 x 2 design, were muscle color (a proxy for heme level), processing temperature, added nitrite, and packaging. Fischer 344 rats were fed these 16 diets, and we evaluated fecal and urinary fat oxidation and cytotoxicity, three biomarkers of heme-induced carcinogenesis promotion. A principal component analysis allowed for selection of four cured meats for inclusion into a promotion study. These selected diets were given for 100 days to rats pretreated with 1,2-dimethylhydrazine. Colons were scored for preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF). Cured meat diets significantly increased the number of ACF/colon compared with a no-meat control diet (P = 0.002). Only the cooked nitrite-treated and oxidized high-heme meat significantly increased the fecal level of apparent total N-nitroso compounds (ATNC) and the number of MDF per colon compared with the no-meat control diet (P < 0.05). This nitrite-treated and oxidized cured meat specifically increased the MDF number compared with similar nonnitrite-treated meat (P = 0.03) and with similar nonoxidized meat (P = 0.004). Thus, a model cured meat, similar to ham stored aerobically, increased the number of preneoplastic lesions, which suggests colon carcinogenesis promotion. Nitrite treatment and oxidation increased this promoting effect, which was linked with increased fecal ATNC level. This study could lead to process modifications to make nonpromoting processed meat.

Figure 1

Principal Components score plot 1 vs 2 (A) and 2 vs 3 (B) related to data the matrix, and principal component loading plot 1 vs 2 (C) and 2 vs 3 (D). Groups are represented by the plot labels Abbreviations of biomarker names: TBARs = TBARs of fecal water; Cytotox. = Cytotoxicity of fecal water, Cytotox. Apc+/+ = Cytotoxicity of fecal water on Apc+/+ cells; Cytotox. Apc+/− = Cytotoxicity of fecal water on Apc+/− cells; Cytotox. CMT = Cytotoxicity of fecal water on CMT93 cells. Abbreviations of diet names: CON-10, control diet; All experimental diets contained 55% processed meat: LCNA, [light cooked meat with nitrite, anaerobic]; DCNA, [dark cooked meat with nitrite, anaerobic]; LRNA, [light raw meat with nitrite, anaerobic]; DRNA, [dark raw meat with nitrite, anaerobic]; LCZA, [light cooked meat, anaerobic]; DCZA, [dark cooked meat, anaerobic]; LRZA, [light raw meat, anaerobic]; DRZA, [dark raw meat, anaerobic]; LCNO, [light cooked meat with nitrite, oxidized]; DCNO, [dark cooked meat with nitrite, oxidized]; LRNO, [light raw meat with nitrite, oxidized]; DRNO, [dark raw meat with nitrite, oxidized]; LCZO, [light cooked meat, oxidized]; DCZO, [dark cooked meat, oxidized]; LRZO, [light raw meat, oxidized]; DRZO, [dark raw meat, oxidized].

Fig. 2

Fecal N-nitroso-compounds (ATNC) in rats given experimental diets for 80d after a 1,2-dimethylhydrazine injection. Values are means ± SD, n = 5. DCNO significantly different from all other groups (P<0.001, n = 5) Diets contained 55% processed meat: DCNO, Dark-Cooked-With Nitrite and Oxidized; DCNA, Dark-Cooked-With Nitrite and kept Anaerobic; DCZA, Dark-Cooked-Without Nitrite Oxidized; DRZA, Dark-Raw-Without Nitrite and kept Anaerobic. Detailed compositions are given in the Material and Methods section. N-nitroso-compounds were assessed as apparent total N-nitroso compounds (ATNC) by Pollock (UK).