Chemoprevention of 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis by the dietary flavonoids chalcone, 2-hydroxychalcone, and quercetin.
Chemoprevention of 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis by the dietary flavonoids chalcone, 2-hydroxychalcone, and quercetin.
复制标题
DOI：
--
复制
发表时间：
1996-11
期刊：
影响因子：
11.2
通讯作者：
H. Makita;Takuji Tanaka;H. Fujitsuka;N. Tatematsu;K. Satoh;A. Hara;H. Mori
中科院分区：
文献类型：
--
作者：
H. Makita;Takuji Tanaka;H. Fujitsuka;N. Tatematsu;K. Satoh;A. Hara;H. Mori
在4-硝基喹啉-1-氧化物(4-NQO)诱发大鼠口腔肿瘤形成的起始和后阶段，研究了饮食中查尔酮、2-羟基查尔酮和槲皮素对大鼠口腔肿瘤形成的影响。6周龄动物随机分为实验组和对照组。在7周龄时，除单独使用试验化学品的动物和未处理的对照组外，所有动物在饮用水中给予4-NQO[20ppm(Ppm)]8周以诱发口腔肿瘤。为了进行化学预防研究，在开始阶段喂食试验化合物，从接触4-NQO前一周开始，给动物组喂食含有500ppm查尔酮、500ppm 2-羟基查尔酮或500ppm槲皮素的饲料，为期10周。停止4-NQO暴露7天后，这些组被切换到基础饮食，并保持这种饮食直到实验结束。在4-NQO停止给药后1周开始进行化学预防研究，4-NQO组和基础日粮组切换到添加试验化学品的日粮中，并维持22周。其他组包括喂食只含500ppm测试化学物质的饲料的大鼠或未处理的大鼠。研究开始32周后，比较不同饮食组舌肿瘤和癌前病变的发生率、舌上皮多胺水平以及用溴脱氧尿嘧啶核苷标记指数估计的细胞增殖活性。在启动阶段或启动后阶段喂食所有测试化学物质均可显著降低舌癌的发生率(降低68-88%；P<；0.05)。饮食中摄入这些化学物质也显著降低了舌鳞状上皮的溴脱氧尿嘧啶核苷标记指数(P<；0.05)。此外，与单独服用4-NQO的大鼠相比，接受4-NQO和测试化学品治疗的大鼠口腔粘膜中的多胺水平降低。这些结果表明，日常食物中存在的黄酮类查尔酮、2-羟基查尔酮和槲皮素对4-NQO诱发的口腔癌有抑制作用，这种抑制作用可能部分与抑制细胞增殖有关。
The modifying effects of dietary exposure of three flavonoids, chalcone, 2-hydroxychalcone, and quercetin, during the initiation and postinitiation phases of oral tumorigenesis initiated with 4-nitroquinoline-1-oxide (4-NQO) were investigated in male F344 rats. At 6 weeks of age, animals were divided into experimental and control groups. At 7 weeks of age, all animals except those treated with test chemicals alone and the untreated control group were given 4-NQO [20 parts/million (ppm)] in the drinking water for 8 weeks to induce oral neoplasms. For chemopreventive study by feeding of test compounds during the initiation phase, groups of animals were given diets containing 500 ppm chalcone, 500 ppm 2-hydroxychalcone, or 500 ppm quercetin for 10 weeks, starting 1 week before 4-NQO exposure. Seven days after stopping 4-NQO exposure, these groups were switched to the basal diet and kept on this diet until the end of the experiment. For chemopreventive study by treatment with test chemicals during the postinitiation phase, starting 1 week after the cessation of 4-NQO administration, the groups given 4-NQO and the basal diet were switched to the diets mixed with test chemicals and maintained on these diets for 22 weeks. The other groups consisted of rats fed diets containing 500 ppm test chemicals alone or of untreated rats. Thirty-two weeks after the start of the study, the incidence of tongue neoplasms and preneoplastic lesions, polyamine levels in the tongue epithelium, and cell proliferation activity estimated by bromodeoxyuridine labeling index were compared among the different dietary groups. Feeding of all test chemicals during either initiation or postinitiation phases caused a significant reduction in the frequency of tongue carcinoma (68-88% reduction; P < 0.05). Dietary administration of these test chemicals also significantly decreased the bromodeoxyuridine labeling index of the tongue squamous epithelium (P < 0.05). In addition, polyamine levels in the oral mucosa were lowered in rats treated with 4-NQO and test chemicals when compared to those given 4-NQO alone. These results indicate that the flavonoids chalcone, 2-hydroxychalcone, and quercetin present in our daily foods have an inhibitory effect on oral carcinogenesis initiated with 4-NQO, and such a modifying effect may be related partly to the suppression of cell proliferation.