Zusman I
Laboratory of Teratology and Experimental Oncology, Koret School of Veterinary Medicine, Faculty of Agriculture, Food and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot, Israel.
In Vivo. 1998 Nov-Dec;12(6):675-89.
The role of two major factors were analyzed in the prevention of experimentally-induced cancers: a) vaccination of animals with polyclonal IgG generated against the soluble p53 antigen and b) feeding of animals with diets rich with dietary fibers or fat. a) In vaccination, a few attempts have been made to utilize p53 protein as a tumor suppressor. IgG generated against the cytoplasmic, soluble p53 antigen from tumor-bearing rats prevents the carcinogenic effect of 1,2-dimethylhydrazine (DMH) decreasing significantly the number of tumor-bearing rats in vaccinated group compared with non vaccinated controls and preventing benign tumors from becoming malignant. The antitumor effect of vaccination is accompanied by a significant increase in the serum-level of p53 antigen in vaccinated rats compared with non vaccinated controls. The immune response of a host to vaccination activates the lymph components of the spleen, and this activation is manifested by the multiplication of the number of lymphocytes which are generated against specific antigens. This multiplication is achieved by the higher division of the antigen-specific lymphoblasts with their subsequent transformation into plasma cells. These cells synthesize the specific protein (IgG). One such protein is the tumor-associated p53 protein, which is synthesized by rats against rabbit anti-p53 IgG. b) The role of dietary factors in the prevention of chemically induced cancer was reviewed on two models: the role of high fiber diets in prevention of colon cancer, and the role of high fat diets in the prevention of mammary gland cancer. Experiments in colon cancer showed that 20% cellulose decreased significantly tumor incidence caused by DMH. The tumor-preventive effect of a cellulose diet was accompanied by increased enzyme concentrations, such as ornithine decarboxylase, thymidine kinase and beta-glucuronidase. This effect was accompanied by activation of some cellular mechanisms, i.e. apoptosis, proliferating cell nuclear antigen (PCNA) and p53 protein synthesis. Experiments in mammary glands cancer showed that a 15% olive-oil diet reduced significantly the tumor incidence caused by 9,10-dimethyl-1,2-benzanthracene. The antitumor effect of the olive-oil diet was connected to its content of monounsaturated fatty acids, such as oleic and palmitic acids. The promotive tumorigenic effects of other high-fat diets (avocado, soybeans) were associated with high content of some polyunsaturated fatty acids (linoleic and alpha-linolenic). Different diets have different targets. The effect of the same diet depends on its anti-tumor substances content.
Vaccination and some diets have similar mechanism in their tumor-preventive effects.
分析了两个主要因素在预防实验性诱导癌症中的作用:a)用针对可溶性p53抗原产生的多克隆IgG对动物进行疫苗接种,以及b)用富含膳食纤维或脂肪的饮食喂养动物。a)在疫苗接种方面,已经进行了一些尝试来利用p53蛋白作为肿瘤抑制因子。针对荷瘤大鼠细胞质可溶性p53抗原产生的IgG可预防1,2 - 二甲基肼(DMH)的致癌作用,与未接种疫苗的对照组相比,显著降低了接种组荷瘤大鼠的数量,并防止良性肿瘤恶变。与未接种疫苗的对照组相比,接种疫苗的大鼠血清中p53抗原水平显著升高,伴随着疫苗接种的抗肿瘤作用。宿主对疫苗接种的免疫反应激活了脾脏的淋巴细胞成分,这种激活表现为针对特定抗原产生的淋巴细胞数量增加。这种增加是通过抗原特异性淋巴母细胞的更高分裂以及随后转化为浆细胞来实现的。这些细胞合成特定蛋白质(IgG)。一种这样的蛋白质是肿瘤相关p53蛋白,它是大鼠针对兔抗p53 IgG合成的。b)在两种模型上综述了饮食因素在预防化学诱导癌症中的作用:高纤维饮食在预防结肠癌中的作用,以及高脂肪饮食在预防乳腺癌中的作用。结肠癌实验表明,20%的纤维素显著降低了由DMH引起的肿瘤发生率。纤维素饮食的肿瘤预防作用伴随着鸟氨酸脱羧酶、胸苷激酶和β - 葡萄糖醛酸酶等酶浓度的增加。这种作用伴随着一些细胞机制的激活,即细胞凋亡、增殖细胞核抗原(PCNA)和p53蛋白合成。乳腺癌实验表明,15%的橄榄油饮食显著降低了由9,10 - 二甲基 - 1,2 - 苯并蒽引起的肿瘤发生率。橄榄油饮食的抗肿瘤作用与其单不饱和脂肪酸含量有关,如油酸和棕榈酸。其他高脂肪饮食(鳄梨、大豆)的促肿瘤作用与某些多不饱和脂肪酸(亚油酸和α - 亚麻酸)的高含量有关。不同的饮食有不同的靶点。相同饮食的效果取决于其抗肿瘤物质的含量。
疫苗接种和某些饮食在其肿瘤预防作用中具有相似的机制。