A tobacco-specific carcinogen, NNK, enhances AOM/DSS-induced colon carcinogenesis in male A/J mice.
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.
Department of Oncologic Pathology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Mihye
M
Kim
Shingo
S
Miyamoto
Shigeyuki
S
Sugie
Yumiko
Y
Yasui
Rikako
R
Ishigamori-Suzuki
Akira
A
Murakami
Hitoshi
H
Nakagama
Takuji
T
Tanaka
D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D003043:Cocarcinogenesis; D003110:Colonic Neoplasms / Q000139:chemically induced*; D016264:Dextran Sulfate / Q000633:toxicity*; D008297:Male; D051379:Mice; D009602:Nitrosamines / Q000633:toxicity*; D014026:Nicotiana
D002273:Carcinogens; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D016264:Dextran Sulfate; D001397:Azoxymethane