Gurevich P, Ben-Hur H, Sandler B, Berman V, Tendler Y, Zinder O, Zusman I
Laboratory of Experimental Oncology, The Koret School of Veterinary Medicine, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot, Israel.
Int J Mol Med. 1999 Aug;4(2):197-202. doi: 10.3892/ijmm.4.2.197.
The role of the splenic immune system in the development of high sensitivity of p53 transgenic mice to low doses of carcinogen and vaccination was investigated immunohistochemically and morphometrically. Spleens were obtained from human p53 promoter-chloramphenicol acetyl transferase transgenic mice, grouped as follows: 1, untreated controls; 2, exposed to dimethylhydrazine (DMH); 3, and 4, vaccinated with polyclonal antibodies to soluble-53 kDa protein (s53); 5, vaccinated with monoclonal PAb DO1; 6, vaccinated with monoclonal PAb 421; 7, vaccinated with polyclonal alphaH-p53 antibody. Mice in groups 4-7 were treated with DMH after the course of vaccination. Six months later all the mice were tumor-free, but effects of the low dose carcinogen were distinct in the splenic immune system. They were mainly manifested in blast transformation: the total number of lymphocytes and lymphoblasts decreased to 56.5% of the controls. The total of lymphoid cells in the follicles (B zone) and periarterial lymph sheath (T zone) declined, reflecting moderate insufficiency of the spleen's lymphoid system. Vaccination of transgenic mice with antibodies to soluble-p53 elicited mainly a B system response, with lesser T system involvement. Only few signs of B system insufficiency were found in these mice. Vaccination of mice with different antibodies, with subsequent carcinogen treatment, caused changes in the spleen that were similar to those described for DMH alone, but varied with different anti-p53 antibodies. Vaccination with polyclonal antibodies to soluble-p53, or with monoclonal antibodies PAb DO1 or PAb 421, stimulated the splenic activity of T system, and therefore can decrease the tumorigenic effect of carcinogens.
采用免疫组织化学和形态计量学方法，研究了脾脏免疫系统在p53转基因小鼠对低剂量致癌物高敏感性及疫苗接种过程中的作用。从人p53启动子-氯霉素乙酰转移酶转基因小鼠获取脾脏，分组如下：1，未处理对照组；2，暴露于二甲基肼（DMH）；3和4，接种针对可溶性53 kDa蛋白（s53）的多克隆抗体；5，接种单克隆PAb DO1；6，接种单克隆PAb 421；7，接种多克隆αH-p53抗体。4-7组小鼠在疫苗接种过程后用DMH处理。6个月后所有小鼠均无肿瘤，但低剂量致癌物的影响在脾脏免疫系统中明显不同。主要表现为母细胞转化：淋巴细胞和淋巴母细胞总数降至对照组的56.5%。滤泡（B区）和动脉周围淋巴鞘（T区）中的淋巴细胞总数下降，反映出脾脏淋巴系统中度不足。用可溶性p53抗体对转基因小鼠进行疫苗接种主要引发B系统反应，T系统参与较少。在这些小鼠中仅发现少量B系统不足的迹象。用不同抗体对小鼠进行疫苗接种，随后进行致癌物处理，导致脾脏发生的变化与单独使用DMH时描述的变化相似，但因抗p53抗体不同而有所差异。用可溶性p53多克隆抗体或单克隆抗体PAb DO1或PAb 421进行疫苗接种，可刺激T系统的脾脏活性，因此可降低致癌物的致瘤作用。
