A tobacco-specific carcinogen, NNK, enhances AOM/DSS-induced colon carcinogenesis in male A/J mice.

Department of Oncologic Pathology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.

To determine whether tobacco-derived carcinogens affect colon carcinogenesis, the effects of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on colon carcinogenesis were examined using an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model. NNK (10 micromol) was administered to male A/J mice by a single intraperitoneal (i.p.) injection and then AOM (10 mg/kg body weight, i.p.) was given 1 week after NNK administration. One week later, the mice received 1.5% (w/v) DSS in their drinking water for 7 days. All animals were sacrificed at week 22 to examine the pathological lesions in the colon and lung. The incidence (80%, p < 0.05) and multiplicity (4.0 +/- 3.6, p < 0.05) of colonic tumors of the NNK + AOM + DSS group were significantly higher than that of the AOM + DSS group (incidence, 40%; and multiplicity, 1.2 +/- 1.7). The differences in incidence and multiplicity of lung tumors were insignificant between these two groups. Our findings may suggest that smoking increases the risk of inflammation-related colon cancer development.

PMID: 18853746 [PubMed - indexed for MEDLINE]