Analysis for expression of apoptosis and cytokines in target mucosal epithelium of large bowel carcinogenesis

用甲氧基甲醇(MAM)醋酸酯和/或1-羟基蒽醌(1-HA)诱导大鼠大肠肿瘤和致癌物暴露的非肿瘤大鼠肠上皮，观察细胞因子的表达。细胞因子TNF-α和IL-1α在致癌物诱导的非肿瘤性上皮中的表达均高于正常上皮。肿瘤组织中细胞因子的表达强于非肿瘤组织。结果表明，细胞因子的表达与大肠癌变之间存在相互关系。花生四烯酸是由磷脂酶C(PLC)和磷脂酶A_2激活诱导的。我们发现PLC的3种同工酶之一的PLC-Delta在大肠癌变过程中的表达低于非肿瘤组织。这些结果也提示炎性相关酶和细胞因子的表达与大肠细胞的生长或癌变有关。在偶氮甲烷致癌的初期，我们研究了大肠粘膜上皮细胞增殖与细胞凋亡的关系。致癌物暴露后4h即可诱导细胞凋亡，8h达高峰。3d后，细胞凋亡率减少，细胞增殖增加。AOM诱导的细胞凋亡可能与抑制有丝分裂有关。在AOM诱导的细胞毒性的早期阶段，发现增殖细胞核抗原不是细胞增殖的生物标志物，这与细胞周期停滞有关。

Expression of cytokines was examined in methylazoxymethanol (MAM) acetate and/or 1-hydroxyanthraquinone (1-HA)-induced large bowel neoplasms and carcinogen exposed non-neoplastic epithelium of the bowel in rats. Both cytokines of TNF-a and IL-la was more expressed in the carcinogen-initiated non-neoplastic epithelium than in the normal epithelium. The expression of the cytokines in the neoplasms was stronger than in the non-neoplastic epithelium. The results suggest a mutual relationship between the expression of the cytokines and carcinogenesis.Arachidonic acid is induced by activation of phospholipase C (PLC) as well as phospholipase A_2. We discovered that expression of PLC-delta, one of 3 isozymes of PLC of the neoplasms is lower than of the non-neoplastic tissues in the large bowel carcinogenesis of rats. These results also imply that expression of imflammation associated enzymes and cytokines is related to cell growth or carcinogenesis in the large bowel.Relationship between the cell proliferation and the apoptosis was investigated in mucosal epithelium of large bowel on the initial stage of azoxymethane-induced carcinogenesis. Apoptosis was induced 4 hours after the exposure of carcinogen and reached to the peak at after 8 hours. In 3 days, appearance of apoptosis was decreased and increased the cell proliferation reversely. AOM-induced apoptosis appeared to relate to inhibition of mitosis. PCNA was found to be not the biomarker for cell proliferation in the early stage of AOM-induced toxicity which is associated with cell-cycle arrest.