Zusman I, Reifen R, Livni O, Smirnoff P, Gurevich P, Sandler B, Nyska A, Gal R, Tendler Y, Madar Z
Laboratory of Teratology and Experimental Oncology, Koret School of Veterinary Medicine, Israel.
Anticancer Res. 1997 May-Jun;17(3C):2105-13.
The role of apoptosis, proliferative cell nuclear antigen (PCNA) and p53 protein in the preventive effects of dietary fiber treated with the fungus Pleurotus ostreatus on rat-colon tumorigenesis was studied. Tumors were induced by five subcutaneous injections of 1,2-dimethylhydrazine (DMH), 20 mg/kg rat, once a week. Rats were fed a semi-synthetic fiberfree diet (control) or a high-fiber diet (15%) derived from corncob treated or non-treated with the fungus. The rats we sacrificed 24 weeks after the first carcinogenic injection. The fungus treated corn-cob significantly decreased tumor incidence (to 26%) as compared to 44% and 57% in the other dietary groups. The apoptotic index (AI) significantly decreased in malignant tissue as compared to non-tumorous tissue. PCNA and cytoplasmic content of p53 protein exhibited an increasing trend in malignant tissue as compared to benign tissue (at 15% and 18%, respectively). The fungus-treated corncob significantly increased the content of p53 in the cell cytoplasm (to 33%) and its serum levels in tumor-bearing rats (to 38%). The cellular concentration of PCNA decreased to 61% in tumors obtained from rats fed the fungus-treated corncob as compared to controls. A high positive correlation was found between tumor grade and p53 protein in the serum (r = 0.97) or in the cell cytoplasm (r = 0.77) and between tumor grade and PCNA (r = 0.81). An inverse relationship was found between tumor grade and AI (r = -0.63). We found that 15% of corncob fiber alone seems not to be enough to prevent chemically induced tumorigenesis. The corncob fiber (15%) treated with the fungus had a significant protective effect against DMH-induced rat colon cancer, even at 15% and this effect was accompanied by the activation of some cellular mechanisms such as apoptosis, PCNA and p53 protein activation. Incubation of corncob with the fungus Pleurotus os, increased the dietary fiber content up to 78%. Thus corncob inhibits colon cancer development, and, therefore, may considered of potential use to the public.
研究了凋亡、增殖细胞核抗原(PCNA)和p53蛋白在经平菇处理的膳食纤维对大鼠结肠癌发生的预防作用中的作用。通过每周一次、连续五次皮下注射1,2 - 二甲基肼(DMH)(20 mg/kg大鼠)诱导肿瘤。给大鼠喂食半合成无纤维饮食(对照)或来源于经或未经真菌处理的玉米芯的高纤维饮食(15%)。在首次致癌注射后24周处死大鼠。与其他饮食组的44%和57%相比,经真菌处理的玉米芯显著降低了肿瘤发生率(降至26%)。与非肿瘤组织相比,恶性组织中的凋亡指数(AI)显著降低。与良性组织相比(分别为15%和18%),恶性组织中PCNA和p53蛋白的细胞质含量呈上升趋势。经真菌处理的玉米芯显著增加了荷瘤大鼠细胞质中p53的含量(增至33%)及其血清水平(增至38%)。与对照组相比,喂食经真菌处理玉米芯的大鼠肿瘤中PCNA的细胞浓度降至61%。在肿瘤分级与血清中p53蛋白(r = 0.97)或细胞质中p53蛋白(r = 0.77)以及肿瘤分级与PCNA之间(r = 0.81)发现高度正相关。在肿瘤分级与AI之间发现负相关(r = -0.63)。我们发现单独15%的玉米芯纤维似乎不足以预防化学诱导的肿瘤发生。经真菌处理的15%玉米芯纤维对DMH诱导的大鼠结肠癌具有显著的保护作用,即使在15%的比例下,这种作用伴随着一些细胞机制的激活,如凋亡、PCNA和p53蛋白的激活。玉米芯与平菇一起培养,使膳食纤维含量增加至78%。因此,玉米芯抑制结肠癌发展,因此可能被认为对公众有潜在用途。