Enhancing effects of simultaneous treatment with sodium nitrite on 2-amino-3-methylimidazo[4,5-f]quinoline-induced rat liver, colon and Zymbal's gland carcinogenesis after initiation with diethylnitrosamine and 1,2-dimethylhydrazine.
Combined effects of sodium nitrite (NaNO2) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) on liver, colon and Zymbal's gland carcinogenesis were assessed using a rat two-stage carcinogenesis model, with a focus on involvement of oxidative stress. Male 6-week-old F344 rats were given a single intraperitoneal injection of 200 mg/kg of diethylnitrosamine and 4 subcutaneous injections of 40 mg/kg of 1,2-dimethylhydrazine for initiation. Then, they were administered 0 or 300 ppm IQ in the diet or 0, 0.1 or 0.2% NaNO2 in their drinking water for 27 weeks. The treatment with NaNO2+IQ significantly enhanced colon and Zymbal's gland carcinogenesis and tended to enhance hepatocarcinogenesis. The incidence of lung tumors in the IQ-treated groups was significantly increased as compared with the initiation alone group. In a second experiment, male rats were given IQ or NaNO2 under the same conditions as before for 1 week, and at sacrifice, their liver and colon tissue or mucosa were collected for analysis of 8-hydroxydeoxyguanosine (8-OHdG), thiobarbituric acid reactive substances (TBARS), acrolein-modified protein and the bromodeoxyuridine-labeling index (BrdU-LI) (in the colon). In the colon, 8-OHdG, acrolein-modified protein levels and BrdU-LI were significantly increased by the combined treatment. These results indicate that the treatment with NaNO2 enhances IQ-induced colon and Zymbal's gland carcinogenesis in rats and that oxidative DNA damage and lipid peroxidation may partly be involved, especially in the colon. In addition, this experiment showed that IQ can act as a potent lung carcinogen in rats.
Kitamura
Yasuki
Y
Division of Pathology, National Institute of Health Sciences, Tokyo 158-8501, and Department of Veterinary Pathology, Faculty of Agriculture, Gifu University, Japan.
Umemura
Takashi
T
Okazaki
Kazushi
K
Kanki
Keita
K
Imazawa
Takayoshi
T
Masegi
Toshiaki
T
Nishikawa
Akiyoshi
A
Hirose
Masao
M
D019813:1,2-Dimethylhydrazine / Q000008:administration & dosage / Q000633:toxicity; D000284:Administration, Oral; D000477:Alkylating Agents / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000503:physiopathology*; D004249:DNA Damage; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000633:toxicity; D004347:Drug Interactions; D007202:Indicators and Reagents / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D015227:Lipid Peroxidation; D008113:Liver Neoplasms / Q000139:chemically induced / Q000503:physiopathology*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D018384:Oxidative Stress; D011804:Quinolines / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012977:Sodium Nitrite / Q000008:administration & dosage / Q000633:toxicity*
D000477:Alkylating Agents; D002273:Carcinogens; D007202:Indicators and Reagents; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D004052:Diethylnitrosamine; D019813:1,2-Dimethylhydrazine; D012977:Sodium Nitrite