Induction of apoptosis by sulindac in azoxymethane-induced possible colonic premalignant lesions in rats.
Induction of apoptosis by sulindac in azoxymethane-induced possible colonic premalignant lesions in rats.
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DOI：
10.1111/j.1349-7006.2002.tb02164.x
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发表时间：
2002-03
期刊：
影响因子：
--
通讯作者：
Mori H
中科院分区：
文献类型：
--
作者：
Kuno T;Yamada Y;Hirose Y;Katayama M;Sakata K;Hara A;Saji S;Mori H
我们报道，β-连环蛋白累积隐窝（BCAC）不具有异常隐窝病灶（ACF）的外观，可能是大鼠结肠癌前病变。抑制此类病变的发生和进展对于癌症预防至关重要。本研究检验了舒林酸（一种化学预防性非甾体抗炎药）是否能够诱导此类癌前病变的细胞凋亡。 6 周龄时，第 1-3 组大鼠每周接受一次氧化偶氮甲烷 (AOM)（15 毫克/公斤体重），持续 3 周。两组从 9 周龄开始在饮食中添加舒林酸（200 和 400 ppm）。在终止时处死大鼠，并仔细检查结肠。 BCAC和ACF的发生率和隐窝复数均显着低于对照组。舒林酸对BCAC表达的影响大于对ACF表达的影响。暴露于舒林酸显着增加了 BCAC 中的凋亡指数（末端脱氧核苷酸转移酶 dUTP 缺口末端标记 (TUNEL) 阳性细胞）。然而，在ACF的情况下，没有发现该指数显着增加。这些结果表明，舒林酸对大鼠的化学预防作用与诱导癌前病变中的细胞凋亡有关。我们的结果还提供了额外的证据，表明 BCAC 是啮齿类动物结肠癌发生过程中的癌前病变。
We have reported that β‐catenin‐accumulated crypts (BCAC), which do not have the appearance of aberrant crypt foci (ACF) are possible colonic premalignant lesions in rats. Suppression of the occurrence and advancement of such lesions should have critical relevance to cancer prevention. This study examined whether sulindac, a chemopreventive nonsteroidal anti‐inflammatory drug is able to induce apoptosis in such premalignant lesions. At 6 weeks of age, rats groups 1–3 were given azoxymethane (AOM) (15 mg/kg‐body weight) once weekly for 3 weeks. Two groups were given sulindac in the diet (200 and 400 ppm), starting at 9 weeks of age. The rats were sacrificed at the termination, and the colons were carefully examined. The incidence and crypt multiplicity of BCAC and ACF were significantly less than those of the control group. The effect of sulindac on the expression of BCAC was greater than that on ACF. Exposure to sulindac significantly increased the apoptotic index (terminal deoxynucleotide transferase dUTP nick‐end labeling (TUNEL)‐positive cells) in BCAC. However, no significant increase of the index was found in the case of ACF. These results suggest that the chemopreventive effect of sulindac in rats is related to the induction of apoptosis in premalignant lesions. Our results also provide additional evidence that BCAC are premalignant lesions in colon carcinogenesis in rodents.
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DOI：
10.1111/j.1349-7006.1989.tb02257.x
发表时间：
1989-11
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Tanaka T;Takeuchi T;Nishikawa A;Takami T;Mori H
通讯作者：
Mori H
DOI：
10.1111/j.1749-6632.1994.tb12037.x
发表时间：
1994-01-01
期刊：
PLATELET-DEPENDENT VASCULAR OCCLUSION
影响因子：
--
作者：
SMITH, WL;MEADE, EA;DEWITT, DL
通讯作者：
DEWITT, DL
DOI：
10.1083/jcb.119.3.493
发表时间：
1992-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gavrieli Y;Sherman Y;Ben-Sasson SA
通讯作者：
Ben-Sasson SA
影响因子：
4.7
作者：
Mahmoud, NN;Boolbol, SK;Bertagnolli, MM
通讯作者：
Bertagnolli, MM
影响因子：
254.7
作者：
Greenlee, RT;Murray, T;Wingo, PA
通讯作者：
Wingo, PA