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姜黄素可改变Apc(min)小鼠的抗凋亡能力,并抑制2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶(PhIP)诱导的Apc(min)小鼠肿瘤形成。

Curcumin modifies Apc(min) apoptosis resistance and inhibits 2-amino 1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induced tumour formation in Apc(min) mice.

作者信息

Collett G P, Robson C N, Mathers J C, Campbell F C

机构信息

Department of Surgery, The Cancer Centre, Queen's University Belfast.

出版信息

Carcinogenesis. 2001 May;22(5):821-5. doi: 10.1093/carcin/22.5.821.

DOI:10.1093/carcin/22.5.821
PMID:11323404
Abstract

Curcumin, the active ingredient of the rhizome of Curcuma longa, promotes apoptosis and may have chemopreventive properties. This study investigates the effects of curcumin on apoptosis and tumorigenesis in male Apc(min) mice treated with the human dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Intestinal epithelial apoptotic index in response to PhIP treatment was approximately twice as great in the wild-type C57BL/6 APC(+/+) strain than in Apc(min) mice (3.7% Apc(+/+) versus 1.9% Apc(min); P < 0.001). PhIP promoted tumour formation in Apc(min) proximal small intestine (4.6 tumours per mouse, PhIP treated versus 2.1 tumours per mouse, control untreated; P < 0.05). Curcumin enhanced PhIP-induced apoptosis (4.0% curcumin + PhIP versus 2.1% PhIP alone; P < 0.01) and inhibited PhIP-induced tumorigenesis in the proximal small intestine of Apc(min) mice (2.2 tumours per mouse, curcumin + PhIP versus 4.6 tumours per mouse PhIP alone; P < 0.05). This study shows that the Apc(min) genotype is associated with resistance to PhIP-induced apoptosis in intestinal epithelium. Curcumin attenuates Apc(min) resistance to PhIP-induced apoptosis and inhibits PhIP-induced tumorigenesis in proximal Apc(min) mouse small intestine.

摘要

姜黄素是姜黄根茎的活性成分,可促进细胞凋亡,可能具有化学预防特性。本研究调查了姜黄素对用人类饮食致癌物2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶(PhIP)处理的雄性Apc(min)小鼠细胞凋亡和肿瘤发生的影响。野生型C57BL/6 APC(+/+)品系对PhIP处理的肠道上皮细胞凋亡指数约为Apc(min)小鼠的两倍(Apc(+/+)为3.7%,Apc(min)为1.9%;P < 0.001)。PhIP促进了Apc(min)小鼠近端小肠肿瘤的形成(PhIP处理组每只小鼠有4.6个肿瘤,未处理的对照组每只小鼠有2.1个肿瘤;P < 0.05)。姜黄素增强了PhIP诱导的细胞凋亡(姜黄素+PhIP组为4.0%,单独使用PhIP组为2.1%;P < 0.01),并抑制了PhIP诱导的Apc(min)小鼠近端小肠肿瘤发生(姜黄素+PhIP组每只小鼠有2.2个肿瘤,单独使用PhIP组每只小鼠有4.6个肿瘤;P < 0.05)。本研究表明,Apc(min)基因型与肠道上皮对PhIP诱导的细胞凋亡的抗性有关。姜黄素减弱了Apc(min)对PhIP诱导的细胞凋亡的抗性,并抑制了PhIP诱导的Apc(min)小鼠近端小肠肿瘤发生。

相似文献

1
Curcumin modifies Apc(min) apoptosis resistance and inhibits 2-amino 1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induced tumour formation in Apc(min) mice.姜黄素可改变Apc(min)小鼠的抗凋亡能力,并抑制2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶(PhIP)诱导的Apc(min)小鼠肿瘤形成。
Carcinogenesis. 2001 May;22(5):821-5. doi: 10.1093/carcin/22.5.821.
2
Intestinal tumours induced by the food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in multiple intestinal neoplasia mice have truncation mutations as well as loss of the wild-type Apc(+) allele.食物致癌物2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶在多发性肠道肿瘤小鼠中诱发的肠道肿瘤具有截短突变以及野生型Apc(+)等位基因的缺失。
Mutagenesis. 2001 Jul;16(4):309-15. doi: 10.1093/mutage/16.4.309.
3
Age at exposure and Apc status influence the levels of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts in mouse intestine and liver.暴露时的年龄和Apc状态会影响小鼠肠道和肝脏中2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶(PhIP)-DNA加合物的水平。
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4
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Mutat Res. 2004 Jan 10;557(1):29-40. doi: 10.1016/j.mrgentox.2003.09.008.
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Impact of genetic background on spontaneous or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced intestinal tumorigenesis in Min/+ mice.遗传背景对Min/+小鼠自发性或2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶(PhIP)诱导的肠道肿瘤发生的影响。
Cancer Lett. 2006 Aug 28;240(2):289-96. doi: 10.1016/j.canlet.2005.09.015. Epub 2005 Dec 15.
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2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces genetic changes in murine intestinal tumours and cells with ApcMin mutation.2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶(PhIP)在携带ApcMin突变的小鼠肠道肿瘤和细胞中诱导基因变化。
Mutat Res. 2006 Apr 30;604(1-2):60-70. doi: 10.1016/j.mrgentox.2006.01.004. Epub 2006 Mar 29.
7
One dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) or 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) induces tumours in Min/+ mice by truncation mutations or LOH in the Apc gene.一剂2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶(PhIP)或2-氨基-3-甲基咪唑并[4,5-f]喹啉(IQ)通过Apc基因的截短突变或杂合性缺失在Min/+小鼠中诱发肿瘤。
Mutat Res. 2002 May 27;517(1-2):157-66. doi: 10.1016/s1383-5718(02)00065-7.
8
Intestinal toxicity and carcinogenic potential of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in DNA repair deficient XPA-/- mice.食物诱变剂2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶(PhIP)在DNA修复缺陷型XPA-/-小鼠中的肠道毒性和致癌潜力。
Carcinogenesis. 2001 Apr;22(4):619-26. doi: 10.1093/carcin/22.4.619.
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Cancer Res. 2001 Dec 15;61(24):8689-96.
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Incorporation of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) into fur and correlation with intestinal tumourigenesis in Min/+ mice.食物诱变剂2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶(PhIP)在Min/+小鼠皮毛中的掺入及其与肠道肿瘤发生的相关性。
Pharmacol Toxicol. 2003 Mar;92(3):131-6. doi: 10.1034/j.1600-0773.2003.920305.x.

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