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Arsenic trioxide exposure accelerates colon preneoplasic aberrant crypt foci induction regionally through mitochondrial dysfunction
Toxicology Research ( IF 2.2 ) Pub Date : 2017-09-27 00:00:00 , DOI: 10.1039/c7tx00213k Hichem Moulahoum 1, 2, 3, 4, 5 , Belkacem Mohamed Amine Boumaza 1, 2, 3, 4, 5 , Meriem Ferrat 1, 2, 3, 4, 5 , Bahia Djerdjouri 1, 2, 3, 4, 5
Toxicology Research ( IF 2.2 ) Pub Date : 2017-09-27 00:00:00 , DOI: 10.1039/c7tx00213k Hichem Moulahoum 1, 2, 3, 4, 5 , Belkacem Mohamed Amine Boumaza 1, 2, 3, 4, 5 , Meriem Ferrat 1, 2, 3, 4, 5 , Bahia Djerdjouri 1, 2, 3, 4, 5
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Arsenic poisoning is a worldwide problem. Thus, we studied the effects of arsenic trioxide (ATO) administration on a 1,2-dimethylhydrazine (DMH)-induced preneoplasic colon carcinogenesis model. Mice were separated into four study groups; the control group received only vehicles. The ATO group received daily a 2.5 mg kg−1 dose for 4 weeks. The DMH group received DMH (20 mg kg−1) twice in two weeks. The third group (D-ATO) had the same as the DMH group with ATO administration starting at week 10. At the end of 14 weeks, colons from sacrificed mice were taken, segmented into distal and proximal and subjected to aberrant crypt foci (ACF), aberrant crypt (AC) counting, alcian blue, H&E and Hoechst histological study and lastly oxidative stress marker analysis as well as mitochondrial swelling assessment. Data showed a significant increase in ACF and AC after DMH treatment, which was further increased after ATO addition. A perturbed histological structure was observed and loss of mucin producing cells in the colon tissue was observed. An important impact on the distal colon compared to the proximal one was noticed. The oxidative stress balance showed a similar pattern with an increase in MPO, NO/L-ornithine balance and MDA, while a decrease was observed in the antioxidant enzymes (CAT, SOD and GSH). In all parameters analyzed, the distal colons showed higher values than proximal. Furthermore, histological cell death analysis in combination with mitochondrial permeability pore opening suggested ATO contribution in the pathological effect. Our study has shown that ATO administration accelerated colon cancer development suggesting the heaviness of such treatments and the need to explore combinations and cycle type formulas.
中文翻译：
三氧化二砷暴露通过线粒体功能障碍局部加速结肠新肿瘤前隐窝病灶的诱导
砷中毒是一个世界性的问题。因此，我们研究了三氧化二砷（ATO）施用对1,2-二甲基肼（DMH）诱导的新肿瘤前结肠癌发生模型的影响。将小鼠分成四个研究组。对照组只收到车辆。ATO组每天接受2.5 mg kg -1剂量的剂量，持续4周。DMH组接受DMH（20 mg kg -1）在两周内两次。第三组（D-ATO）与DMH组相同，从第10周开始进行ATO给药。在14周结束时，从处死小鼠中取出结肠，将其分成远端和近端，并进行异常的隐窝灶（ACF） ），异常隐窝（AC）计数，阿尔辛蓝，H＆E和Hoechst组织学研究，最后进行氧化应激标记分析以及线粒体肿胀评估。数据显示，DMH处理后，ACF和AC显着增加，而添加ATO后，ACF和AC显着增加。观察到扰动的组织学结构，并观察到结肠组织中产生粘蛋白的细胞的丢失。注意到与近端结肠相比，对远端结肠有重要影响。氧化应激平衡表现出相似的模式，MPO，NO / L升高-鸟氨酸平衡和MDA，而抗氧化酶（CAT，SOD和GSH）则下降。在所有分析的参数中，远端结肠显示出比近端更高的值。此外，结合线粒体通透性孔的组织细胞死亡分析表明，ATO在病理作用中的作用。我们的研究表明，使用ATO可以加速结肠癌的发展，这表明此类疗法的繁重性以及探索组合和周期类型公式的必要性。
更新日期：2017-09-27
中文翻译：
三氧化二砷暴露通过线粒体功能障碍局部加速结肠新肿瘤前隐窝病灶的诱导
砷中毒是一个世界性的问题。因此，我们研究了三氧化二砷（ATO）施用对1,2-二甲基肼（DMH）诱导的新肿瘤前结肠癌发生模型的影响。将小鼠分成四个研究组。对照组只收到车辆。ATO组每天接受2.5 mg kg -1剂量的剂量，持续4周。DMH组接受DMH（20 mg kg -1）在两周内两次。第三组（D-ATO）与DMH组相同，从第10周开始进行ATO给药。在14周结束时，从处死小鼠中取出结肠，将其分成远端和近端，并进行异常的隐窝灶（ACF） ），异常隐窝（AC）计数，阿尔辛蓝，H＆E和Hoechst组织学研究，最后进行氧化应激标记分析以及线粒体肿胀评估。数据显示，DMH处理后，ACF和AC显着增加，而添加ATO后，ACF和AC显着增加。观察到扰动的组织学结构，并观察到结肠组织中产生粘蛋白的细胞的丢失。注意到与近端结肠相比，对远端结肠有重要影响。氧化应激平衡表现出相似的模式，MPO，NO / L升高-鸟氨酸平衡和MDA，而抗氧化酶（CAT，SOD和GSH）则下降。在所有分析的参数中，远端结肠显示出比近端更高的值。此外，结合线粒体通透性孔的组织细胞死亡分析表明，ATO在病理作用中的作用。我们的研究表明，使用ATO可以加速结肠癌的发展，这表明此类疗法的繁重性以及探索组合和周期类型公式的必要性。
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