Abstract 3446: Induction of colonic aberrant crypts in mice by an apparent N-nitroso compound fraction derived from hot dogs

Abstract

Abstract Introduction: Nitrite-preserved meat products, e.g., hot dogs, may be a cause of colon cancer. This may occur because such products contain a possibly carcinogenic fraction called “total apparent N-nitroso compounds” (ANC). Feeding such products to humans and mice increased the fecal excretion of ANC. We tested here whether hot-dog-derived ANC could induce colonic aberrant crypts (ABC), a precursor lesion for colon cancer, in mice. Methods: We purified the ANC precursor (ANCP) fraction of commercial hot hogs by adsorption-desorption on silica gel and cation exchange resin, and treated the ANCP with nitrite to convert them to ANC. As a positive control group, adult female A/J mice were given 1 or 3 i.p. injections of 5 mg/kg of azoxymethane (AOM) [Experiment (Exp.) 1]. In Exps. 2 and 3, similar mice were continuously fed the purified hot dog ANC (initial dose, 100 nmol/g diet) in a high-fat or “high-fat stress” diet. In Exp. 2 the ANC dose initially dropped sharply, probably because the ANCP was unstable on thawing, but later in Exp 2 and throughout Exp 3 the ANCP level was stable and was maintained at 100 nmol/g diet. The mice were killed after 8 (for AOM tests) or 24-34 (for ANC tests) weeks of treatment. Feces of the ANC-treated mice contained up to 225 nmol ANC/g, indicating that the ANC reached the colon. The distal 2 cm of each colon was stained with methylne blue, the mucosal surfaces were scanned at 400 x magnification, and ABC were identified and counted. Results: Mean numbers of ANC/colon for 1 and 3 AOM injections, AOM controls, ANC (Exp 2), ANC (Exp. 3) and ANC controls were 28, 76, 14, 20, 14 and 5-8. Standard deviations were <50% of mean values. The effect of ANC was significant by the rank order test (P < 0.01) for both Exps. 2 and 3. Potency of ABC induction per mole ANC was 1.7% (Exp. 2) and 0.4% (Exp. 3) of that for AOM in Exp. 1. In Exp. 3 we noted that the ABC occurred as foci with 1-4 ABC/focus and a mean of 6.8 foci/colon. ANC treatment did not affect the number of foci. Conclusions: Hot-dog-derived ANC induced a significant number of ABC in the mouse colon, but the effect was relatively weak. These results provide a direct link between ANC in a nitrite-preserved meat product and effects in the colon. Partly supported by NIH grant RO1 CA-143460-01. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3446.