Kossoy George, Zandbank Judit, Tendler Eugenie, Anisimov Vladimir, Khavinson Vladimir, Popovich Irina, Zabezhinski Mark, Zusman Itshak, Ben-Hur Herzl
Laboratory of Experimental Medicine, Rehovot, Israel.
Int J Mol Med. 2003 Oct;12(4):473-7.
The effect of the synthetic pineal peptide Epitalon (Ala-Glu-Asp-Gly) on proliferative activity in colon tumors, and in mucosal epithelial cells adjacent to and located far from tumors was studied in rats. To evaluate the effect of Epitalon on different stages of carcinogenesis, different treatment regimens were used: during the tumor initiation stage, during the tumor-promotion stage, or during the entire process of tumor development. Eighty 2-month-old male LIO rats were exposed weekly to five subcutaneous injections of 1,2-dimethylhydrazine (DMH) at a single dose of 21 mg/kg body weight. Rats were divided into four groups. Control rats (group 1) received saline at a dose of 0.1 ml during the entire experiment. Rats in group 2 were treated with Epitalon at a dose of 1 micro g, five times a week, for 6 months, from the first injection of DMH till the end of the experiment. Rats in group 3 were treated with Epitalon after termination of the carcinogen injections. Rats in group 4 were treated with Epitalon only during the period of DMH exposure (for the first 5 weeks of the experiment). DMH induced proliferation of the secretory epithelium, and this phenomenon was accompanied by a decrease in the size of the stromal area and the area of lymph infiltration in colon tumors and in the colon mucosa adjacent to the tumors (group 1). Epitalon attenuated this effect, especially when the treatment was continued throughout the experiment (group 2). It increased the stromal areas, as well as that of lymphoid infiltration in the colon mucosa adjacent to the tumors. The intensity of lymphoid infiltration was activated in both the colon mucosa adjacent to a tumor and in the tumor. Mitotic activity of tumor cells was significantly inhibited by Epitalon when the treatment was given throughout the experiment (group 2). In parallel, a high level of apoptosis was seen in the same group. Thus, the strongest inhibitory effect of Epitalon on carcinogenesis in the colon mucosa was manifested when the treatment was continued throughout the experiment.
在大鼠中研究了合成松果体肽埃替拉肽（Ala-Glu-Asp-Gly）对结肠肿瘤以及肿瘤附近和远离肿瘤的黏膜上皮细胞增殖活性的影响。为评估埃替拉肽对致癌作用不同阶段的影响，采用了不同的治疗方案：在肿瘤起始阶段、肿瘤促进阶段或肿瘤发展的整个过程中进行治疗。80只2月龄雄性LIO大鼠每周接受5次皮下注射1,2-二甲基肼（DMH），单次剂量为21 mg/kg体重。大鼠被分为四组。对照组大鼠（第1组）在整个实验过程中接受0.1 ml剂量的生理盐水。第2组大鼠从首次注射DMH直至实验结束，每周5次接受剂量为1μg的埃替拉肽治疗，持续6个月。第3组大鼠在致癌物注射终止后接受埃替拉肽治疗。第4组大鼠仅在DMH暴露期间（实验的前5周）接受埃替拉肽治疗。DMH诱导分泌上皮细胞增殖，这种现象伴随着结肠肿瘤以及肿瘤附近结肠黏膜中基质面积和淋巴浸润面积的减小（第1组）。埃替拉肽减弱了这种作用，尤其是当整个实验过程中持续治疗时（第2组）。它增加了肿瘤附近结肠黏膜中的基质面积以及淋巴浸润面积。肿瘤附近结肠黏膜和肿瘤中的淋巴浸润强度均被激活。当整个实验过程中给予治疗时，埃替拉肽显著抑制肿瘤细胞的有丝分裂活性（第2组）。同时，在同一组中观察到高水平的细胞凋亡。因此，当整个实验过程中持续治疗时，埃替拉肽对结肠黏膜致癌作用的抑制效果最为显著。
