Inhibition of oral carcinogenesis by the arotinoid mofarotene (Ro 40-8757) in male F344 rats.
Inhibition of oral carcinogenesis by the arotinoid mofarotene (Ro 40-8757) in male F344 rats.
复制标题
类胡萝卜素莫法罗汀 (Ro 40-8757) 对雄性 F344 大鼠口腔癌的抑制作用。
DOI：
10.1093/carcin/16.8.1903
复制
发表时间：
1995
期刊：
影响因子：
4.7
通讯作者：
A. Hara
中科院分区：
文献类型：
--
作者：
T. Tanaka;H. Makita;M. Ohnishi;H. Mori;K. Satoh;A. Hara
在雄性 F344 大鼠中研究了在 4-硝基喹啉 1-氧化物 (4-NQO) 诱导的口腔癌发生的起始阶段，通过饮食给予新型类胡萝卜素莫法罗汀 (Ro 40-8757) 的化学预防作用，该类药物在极性端基中含有吗啉结构。此外，还评估了该化合物对靶上皮细胞中多胺水平（增殖生物标志物）、5-溴脱氧尿苷标记指数和银染核仁组织区蛋白 (AgNOR)/细胞核数量的调节作用。给大鼠喂食浓度为 250 和 500 p.p.m. 的 Ro 40-8757。 10周。开始饮食一周后，在饮用水中添加 4-NQO（20 p.p.m.），持续 8 周。与单独使用 4-NQO 治疗的大鼠相比，饲喂两种剂量的 Ro 40-8757 可使舌肿瘤（鳞状细胞乳头状瘤和癌）的发生率在 32 周内降低 78%（P < 0.05）。同样，在用 4-NQO 与 Ro 40-8757 一起治疗的大鼠中，癌前病变（增生和发育不良）的发生率显着低于单独使用 4-NQO 的组（P < 0.05）。 Ro 40-8757 的饮食治疗也显着降低了三种生物标志物的表达。因此，当与致癌物同时给药时，一种新的类胡萝卜素 Ro 40-8757 可以抑制 4-NQO 诱导的口腔癌发生。这些结果可能表明，除了乳腺癌之外，Ro 40-8757 还可用于口腔癌症化学预防。
The chemopreventive effect of dietary administration of a new arotinoid, mofarotene (Ro 40-8757), which contains a morpholine structure in the polar end group, during the initiation phase of 4-nitroquinoline 1-oxide (4-NQO)-induced oral carcinogenesis was investigated in male F344 rats. Also, modulatory effects of this compound on polyamine levels (biomarkers of proliferation), the 5-bromodeoxyuridine-labeling index and the number of silver stained nucleolar organizer region proteins (AgNORs)/nucleus were assessed in the target epithelium. Rats were fed Ro 40-8757 at concentrations of 250 and 500 p.p.m. for 10 weeks. One week after the commencement of the diets, 4-NQO (20 p.p.m.) was administered in the drinking water for 8 weeks. Feeding of Ro 40-8757 at both doses caused a 78% reduction in the incidence of tongue neoplasms (squamous cell papilloma and carcinoma) by 32 weeks when compared with rats treated with 4-NQO alone (P < 0.05). Similarly, in rats treated with 4-NQO together with Ro 40-8757 the incidence of preneoplastic lesions (hyperplasia and dysplasia) was significantly less than the 4-NQO alone group (P < 0.05). Expression of three biomarkers was also decreased significantly by dietary treatment with Ro 40-8757. Thus a new arotinoid, Ro 40-8757, inhibited the oral carcinogenesis induced by 4-NQO when it was administered concurrently with the carcinogen. These results might suggest the possible application of Ro 40-8757 for cancer chemoprevention in the oral cavity, in addition to the breast.