Suggestive evidence for the induction of colonic aberrant crypts in mice fed sodium nitrite

abstract

A reported linkage between processed (nitrite-treated) meat products and the incidence of colon cancer could be due to sodium nitrite (NaNO₂) itself or to N-nitroso compounds produced from the nitrite. Exposure to nitrite occurs due to residual nitrite in processed meat and to salivary nitrite arising by reduction of nitrate in vegetables and drinking water. Here we tested whether NaNO₂ could induce colonic aberrant crypts (ABC) or ABC foci (ACF), which are putative precursors of colon cancer. We fed NaNO₂ in drinking water for 20–25 wk to groups of 8–20 adult female mice. After sacrifice, ABC and ACF were counted in 2-cm distal colonic segments. In Experiment 1, no significant differences in ABC/ACF induction were seen between groups of 13–14 A/J mice fed 0, 0.5, or 1.0 g NaNO₂/l drinking water. NaNO₂ also did not affect fasting blood glucose levels. In Experiment 2, we fed 0, 1.0, 1.25, or 1.5 g NaNO₂/l water to groups of 15 CF-1 mice. Five of the mice fed 1.5 g NaNO₂/l showed ABC, whereas all other groups showed only 0–2 ABC/group, including 0 ABC for the group fed 1.25 g NaNO₂/l. Overall statistical analysis indicated a dose-response p trends of 0.04. Pairwise comparison of ABC between groups fed 1.25 and 1.5 g NaNO₂/l showed p 0.02 for both ABC and ACF, but a similar comparison between the untreated and 1.5 g/l groups showed no significant effects. In Experiment 3, hot dogs (18% of diet), which were fed to CF-1 mice previously treated with azoxymethane, inhibited ABC and ACF induction, but this effect was not significant (P = 0.10–0.12). In conclusion, these results support the view that NaNO₂ may be a risk factor for colon carcinogenesis.

Acknowledgments

This article is dedicated to the memory of Dr. Mirvish for his outstanding research on N-nitrosamines. He died August 23, 2015 at the age of 86. He remained active in research until a week before his untimely death. We thank N.E. Sarvetnick (Surgery-Transplant Section, College of Medicine, University of Nebraska Medical Center) for her help in measuring fasting blood glucose levels.

Additional information

Funding

This study was supported by grant RO1-CA-143460 and University of Nebraska Medical Center Eppley and Fred and Pamela Buffett Cancer Center Support Grant 2P30CA036727, both from the National Institutes of Health.