Zusman I, Zusman R, Gurevich P, Korol D, Tendler Y
REG HOSP,NAHARIYYA,ISRAEL.
Oncol Rep. 1996 Sep;3(5):975-9. doi: 10.3892/or.3.5.975.
We have shown the different effects of rabbit IgG generated against various types of p53 tumor-associated protein on chemically induced colon cancer in rats. p53 protein was isolated in the form of cytoplasmic, soluble, protein from sera obtained from: a) rats with colon cancer and b) rats with benign colon tumors. The isolation was performed using the affinity chromatography columns with,eel fiberglass membranes. Anti-p53 IgG were obtained from rabbits vaccinated with the above mentioned types of p53. Sprague Dawley rats were vaccinated with anti-p53 IgG (100 mu g/rat) at two-week intervals for 2 months and then monthly for 3 months. The induction of colon cancer was caused by weekly injections with 1,2-dimethylhydrazine (20 mg/kg) for 7 weeks and was initiated 8 weeks after the start of the vaccination. Results of experiments were evaluated 6 months after the start of cancer induction. It was found that vaccination of rats with IgG generated against the p53 protein isolated from cancer-bearing rats did not exhibit significant protective effect. Only IgG generated against p53 protein from benign tumor-bearing rats significantly prevented the carcinogenic effect of DMH. The number of tumor-bearing rats in vaccinated group decreased to 44% as compared with 93% in the control group. In vaccinated rats, the number of tumors/rat was 0.8 as compared to 9.3 in controls. The number of malignant tumors in vaccinated rats was half that in controls: 29% and 58%, respectively. In the controls, metastases were found in 6 of 45 rats (13%). Anti-p53 IgG not only has an anti-tumor effect but also prevented benign tumors from becoming malignant. We suggest that the anticancer role of a vaccine generated against p53 protein from benign tumor-bearing rats is related to a wild-type p53 protein. Further studies will be performed to clarify this hypothesis.
我们已经展示了针对各种类型p53肿瘤相关蛋白产生的兔IgG对大鼠化学诱导结肠癌的不同影响。p53蛋白以细胞质可溶性蛋白的形式从以下血清中分离得到：a）患有结肠癌的大鼠和b）患有良性结肠肿瘤的大鼠。分离使用带有鳗玻璃纤维膜的亲和色谱柱进行。抗p53 IgG是从用上述类型p53免疫的兔子中获得的。将Sprague Dawley大鼠每隔两周用抗p53 IgG（100μg/只大鼠）免疫2个月，然后每月免疫3个月。结肠癌的诱导是通过每周注射1,2 - 二甲基肼（20mg/kg）持续7周，并在免疫开始8周后开始。在癌症诱导开始6个月后评估实验结果。发现用针对从荷癌大鼠分离的p53蛋白产生的IgG免疫大鼠没有表现出显著的保护作用。只有针对来自荷良性肿瘤大鼠的p53蛋白产生的IgG显著预防了DMH的致癌作用。与对照组的93%相比，免疫组中荷瘤大鼠的数量减少到44%。在免疫大鼠中，每只大鼠的肿瘤数量为0.8，而对照组为9.3。免疫大鼠中的恶性肿瘤数量是对照组的一半：分别为29%和58%。在对照组中，45只大鼠中有6只（13%）发现有转移。抗p53 IgG不仅具有抗肿瘤作用，还能防止良性肿瘤恶变。我们认为，针对来自荷良性肿瘤大鼠的p53蛋白产生的疫苗的抗癌作用与野生型p53蛋白有关。将进行进一步研究以阐明这一假设。
