The effect of lithocholic acid on proliferation and apoptosis during the early stages of colon carcinogenesis: differential effect on apoptosis in the presence of a colon carcinogen
The effect of lithocholic acid on proliferation and apoptosis during the early stages of colon carcinogenesis: differential effect on apoptosis in the presence of a colon carcinogen
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DOI：
10.1093/carcin/21.5.999
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发表时间：
2000-05-01
期刊：
影响因子：
4.7
通讯作者：
Rigas, B
中科院分区：
文献类型：
--
作者：
Kozoni, V;Tsioulias, G;Rigas, B
石胆酸(LCA)与人类和实验动物的致癌作用有关。在1，2-二甲基肼(DMH)诱导的小鼠癌变模型中，观察了四组小鼠(对照组、LCA、DR、IH和DMH+LCA)在癌变早期的4周时间。免疫组织化学方法检测结肠组织细胞凋亡率(AI)和增殖指数(PT)。LCA促进细胞凋亡[AI=1.2+/-0.3%，均值为+/-0.3%]，对照组为0.5+/-0.1%，P<0.05；DMH为4.3+/-0.8%，P<；0.02。在接受DR IH的小鼠中，DMH使隐窝底部的细胞凋亡增加近50倍，对腔三分之一没有影响，LCA几乎完全抑制了细胞凋亡(0.1+/-0.03%)；这种抑制在隐窝的下三分之二(AI=0)和腔三分之一完全抑制(AI=0)和60%。LCA促进细胞增殖(PI=22.2+/-4.6%，对照组为15.4+/-1%)，但无统计学意义。DMH促进增殖(PI=34.6+/-2.3%，P<；0.01)，在接受DMH的小鼠中，增殖(41+/-2.9%)约为相加效应的三分之二。LCA影响增殖，主要在隐窝的中段；DMH的作用在分布上相似，但更明显。在接受DMH的小鼠中，LCA将增殖向上转移，延伸到隐窝的三分之一腔内，LCA在结肠中的主要细胞动力学效应是对细胞凋亡的影响；这种效应在正常(刺激)和癌前病变(几乎完全抑制)中不同。LCA对正常或癌前病变结肠的增殖无明显刺激作用。在存在致癌物的情况下，LCA对细胞凋亡的不同作用部分解释了其作为促进剂在动物模型中的结肠癌发生的作用，并可能对人类的癌变具有重要的意义。
Lithocholic acid (LCA) is implicated in human and experimental animal carcinogenesis. Its effect on apoptosis and proliferation of the colonic epithelium was studied in a 1,2-dimethylhydrazine (DMH)-induced murine carcinogenesis model, Four groups of mice, control, LCA, DR;IH and DMH+LCA, were studied for 4 weeks, a period corresponding to early stages of carcinogenesis. Apoptosis (AI) and proliferation (PT) indices in the colon were determined by immunohistochemistry. LCA stimulated apoptosis [AI = 1.2 +/- 0.3% tall values are the mean +/- SEM) versus control 0.5 +/- 0.1%, P < 0.05], as did DMH (4.3 +/- 0.8%, P < 0.02). DMH increased apoptosis at the base of the crypt nearly 50-fold, with no effect at the lumenal third, In mice receiving DR IH, LCA suppressed apoptosis almost completely (0.1 +/- 0.03%); this suppression was complete at the lower two-thirds of the crypt (AI = 0) and 60% at the lumenal third. LCA increased proliferation (PI = 22.2 +/- 4.6% versus 15.4 +/- 1% in controls), but this did not reach statistical significance. DMH increased proliferation (PI = 34.6 +/- 2.3%, P < 0.01), In mice receiving DMH, proliferation (41 +/- 2.9%) was about two-thirds of the additive effect. LCA affected proliferation, mainly in the middle third of the crypt; DMH's effect was similar in distribution, but more pronounced. In mice receiving DMH, LCA shifts proliferation upward, extending it to the lumenal third of the crypt, LCA's main cell kinetic effect in the colon is on apoptosis; this effect differs in normal (stimulation) and pre-malignant colon (nearly complete suppression). LCA does not significantly stimulate proliferation in either normal or pre-malignant colon. The differential effect of LCA on apoptosis in the presence of a carcinogen partially explains its effect as a promoter on colon carcinogenesis in animal models, and may have important implications for human carcinogenesis.