title: 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.
authors.affiliation: a Eppley Institute for Research in Cancer, University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: b Department of Environmental , Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Zahid
authors.affiliation: a Eppley Institute for Research in Cancer, University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Anwar
authors.affiliation: c Department of Pathology and Microbiology , University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Pennington
authors.affiliation: c Department of Pathology and Microbiology , University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Cohen
authors.affiliation: c Department of Pathology and Microbiology , University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Wisecarver
authors.affiliation: d Department of Statistics , College of Public Health, University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Shostrom
authors.affiliation: a Eppley Institute for Research in Cancer, University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Sidney S
authors.initials: SS
authors.lastname: Mirvish
mesh_terms: D058739:Aberrant Crypt Foci / Q000139:chemically induced*; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D015179:Colorectal Neoplasms / Q000139:chemically induced*; D005260:Female; D006427:Hemin / Q000633:toxicity; D051379:Mice; D012977:Sodium Nitrite / Q000633:toxicity*
chemical_list: D006427:Hemin; D012977:Sodium Nitrite; D001397:Azoxymethane