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
✍ Scribed by Yasuki Kitamura; Takashi Umemura; Kazushi Okazaki; Keita Kanki; Takayoshi Imazawa; Toshiaki Masegi; Akiyoshi Nishikawa; Masao Hirose
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- French
- Weight
- 150 KB
- Volume
- 118
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
Combined effects of sodium nitrite (NaNO~2~) 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% NaNO~2~ in their drinking water for 27 weeks. The treatment with NaNO~2~ + 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 NaNO~2~ 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 NaNO~2~ 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. © 2005 Wiley‐Liss, Inc.