Takeuchi Hijiri, Saoo Kousuke, Yamakawa Keiko, Matsuda Yoko, Yokohira Masanao, Zeng Yu, Kuno Totshiya, Totsuka Yukari, Takahashi Mami, Wakabayashi Keiji, Imaida Katsumi
Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, Kagawa 761-0793.
Oncol Lett. 2010 Jan;1(1):137-142. doi: 10.3892/ol_00000025. Epub 2010 Jan 1.
It has been reported that 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) induces liver tumors and to a lesser extent lung lesions, lymphomas and leukemias in CDF(1) mice. Since a number of case control studies have pointed to a positive association between fat consumption and lung cancer, we examined the lung carcinogenic potential of MeIQx treatment concomitant with a high-fat diet using female A/J mice. Groups 1 and 2 were fed a diet supplemented with MeIQx at a concentration of 600 ppm. Groups 1 and 3 received a diet containing 20% corn oil and group 4 was fed the basal diet alone. After 1 week, 10 mice in each group were sacrificed for measurement of cytochrome P450 (CYP)1A2 mRNA in the liver and lung. The remaining mice were maintained on their respective diets until termination, 32 weeks after the initial MeIQx treatment, when lung proliferative lesions were analyzed. The incidences and multiplicities of hyperplasias and adenomas in MeIQx-treated groups (groups 1 and 2) were significantly higher than in the groups without MeIQx treatment, with a significant increase in the incidences and multiplicities of adenomas + carcinomas, as well as hyperplasia + adenomas + carcinomas (lung proliferative lesions). Lung carcinomas were observed in 1 mouse in each of the MeIQx-treated groups. However, the high-fat diet (groups 1 and 3) did not affect the incidences or multiplicities of lung proliferative lesions. Expression levels of CYP1A2 mRNA after MeIQx treatment significantly increased >3-fold in livers, but no significant change was noted in the lungs, where levels were very low at 1/210 and 1/923 the values for livers. In conclusion, following a 32-week period, we confirmed the lung tumorigenic potential of MeIQx which possibly occurs due to proximate carcinogens activated by CYP1A2 in the liver. However, we failed to detect any influence of a high-fat diet.
据报道，2-氨基-3,8-二甲基咪唑并[4,5-f]喹喔啉（MeIQx）可诱导CDF(1)小鼠发生肝肿瘤，并在较小程度上诱发肺部病变、淋巴瘤和白血病。由于多项病例对照研究表明脂肪摄入与肺癌之间存在正相关，我们使用雌性A/J小鼠研究了MeIQx处理并同时给予高脂饮食时的肺致癌潜力。第1组和第2组喂食添加浓度为600 ppm MeIQx的饮食。第1组和第3组接受含20%玉米油的饮食，第4组仅喂食基础饮食。1周后，每组处死10只小鼠，用于测量肝脏和肺中细胞色素P450（CYP）1A2 mRNA。其余小鼠继续按各自饮食喂养直至实验结束，即首次给予MeIQx处理后32周，此时对肺部增殖性病变进行分析。MeIQx处理组（第1组和第2组）中增生和腺瘤的发生率及数量显著高于未进行MeIQx处理的组，腺瘤+癌以及增生+腺瘤+癌（肺部增殖性病变）的发生率和数量也显著增加。在每个MeIQx处理组中均观察到1只小鼠发生肺癌。然而，高脂饮食（第1组和第3组）并未影响肺部增殖性病变的发生率或数量。MeIQx处理后，肝脏中CYP1A2 mRNA的表达水平显著增加>3倍，但肺中未观察到显著变化，肺中的水平非常低，仅为肝脏水平的1/210和1/923。总之，经过32周的观察，我们证实了MeIQx的肺致瘤潜力，这可能是由于肝脏中CYP1A2激活了近致癌物所致。然而，我们未检测到高脂饮食的任何影响。
