In vitro DNA-damaging effects of intestinal and related tetrapyrroles in human cancer cells.
In vitro DNA-damaging effects of intestinal and related tetrapyrroles in human cancer cells.
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DOI：
10.1016/j.yexcr.2012.12.003
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发表时间：
2013-02-15
影响因子：
3.7
通讯作者：
Wagner, Karl-Heinz
中科院分区：
文献类型：
--
作者：
Moelzer, Christine;Pfleger, Barbara;Putz, Elisabeth;Rossmann, Antonia;Schwarz, Ursula;Wallner, Marlies;Bulmer, Andrew C.;Wagner, Karl-Heinz
流行病学研究报告循环胆红素浓度与癌症和心血管疾病风险之间存在负相关。结构相关的四吡咯也具有体外抗遗传毒性活性，并可能在恶性肿瘤发生前防止突变。此外，很少有数据表明，四吡咯通过诱导细胞周期阻滞和细胞凋亡发挥抗癌作用。为了进一步研究四吡咯是否引起人类癌细胞中的DNA损伤，在单细胞凝胶电泳测定（SCGE）中对其进行了测试。将八种四吡咯（未结合胆红素、胆红素二月桂酸酯、胆绿素、胆绿素-/胆红素二甲酯、尿胆素、粪胆素和原卟啉）加入培养的Caco 2和HepG 2细胞中，并评估它们对彗星形成（%尾DNA）的影响。流式细胞术评估（细胞凋亡/坏死，细胞周期，细胞内自由基的产生）有助于揭示细胞内作用的潜在机制。将细胞与浓度为0.5、5和17 μM的四吡咯孵育24 h。向细胞中加入300 μM叔丁基过氧化氢作为阳性对照。四吡咯孵育主要导致Caco 2和HepG 2细胞中DNA损伤（彗星形成）增加。浓缩在肠内的四吡咯，包括原卟啉、尿胆素和粪胆素，导致两种细胞系中显著的彗星形成，暗示化合物在消化系统器官内发现的癌细胞中诱导DNA损伤和细胞凋亡。胆色素对DNA的损伤作用很少被研究。因此，在彗星试验中测试了八种四吡咯的DNA损伤作用。为了评估DNA损伤，使用癌细胞，并测量流式细胞术参数。特别是原卟啉、尿胆素和粪胆素显著增加DNA链断裂。氧化应激、细胞周期阻滞和细胞凋亡可能是细胞凋亡的主要机制。
Epidemiological studies report a negative association between circulating bilirubin concentrations and the risk for cancer and cardiovascular disease. Structurally related tetrapyrroles also possess in vitro anti-genotoxic activity and may prevent mutation prior to malignancy. Furthermore, few data suggest that tetrapyrroles exert anti-carcinogenic effects via induction of cell cycle arrest and apoptosis. To further investigate whether tetrapyrroles provoke DNA-damage in human cancer cells, they were tested in the single cell gel electrophoresis assay (SCGE). Eight tetrapyrroles (unconjugated bilirubin, bilirubin ditaurate, biliverdin, biliverdin-/bilirubin dimethyl ester, urobilin, stercobilin and protoporphyrin) were added to cultured Caco2 and HepG2 cells and their effects on comet formation (% tail DNA) were assessed. Flow cytometric assessment (apoptosis/necrosis, cell cycle, intracellular radical species generation) assisted in revealing underlying mechanisms of intracellular action. Cells were incubated with tetrapyrroles at concentrations of 0.5, 5 and 17 μM for 24 h. Addition of 300 μM tertiary-butyl hydroperoxide to cells served as a positive control. Tetrapyrrole incubation mostly resulted in increased DNA-damage (comet formation) in Caco2 and HepG2 cells. Tetrapyrroles that are concentrated within the intestine, including protoporphyrin, urobilin and stercobilin, led to significant comet formation in both cell lines, implicating the compounds in inducing DNA-damage and apoptosis in cancer cells found within organs of the digestive system. ► DNA-damaging effects of bile pigments have been rarely investigated. ► Thus, eight tetrapyrroles were tested for DNA-damaging effects in the comet assay. ► To assess DNA damage, cancer cells were used, and flow cytometry parameters were measured. ► Especially protoporphyrin, urobilin and stercobilin increased DNA strand breaks significantly. ► Mechanisms could include oxidative stress, cell cycle arrest and apoptosis.
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影响因子：
6
作者：
Grimm, Stefanie;Mvondo, Dagmar;Breusing, Nicolle
通讯作者：
Breusing, Nicolle
影响因子：
7.3
作者：
Bulmer, A. C.;Coombes, J. S.;Taylor, S. M.
通讯作者：
Taylor, S. M.
影响因子：
3.6
作者：
Calligaris, Sebastian D.;Bellarosa, Cristina;Tiribelli, Claudio
通讯作者：
Tiribelli, Claudio
DOI：
10.1016/j.mrgentox.2007.01.008
发表时间：
2007-05-18
影响因子：
1.9
作者：
Bulmer, A. C.;Ried, K.;Wagner, K-H
通讯作者：
Wagner, K-H
DOI：
10.2215/cjn.06130710
发表时间：
2011-03-01
影响因子：
9.8
作者：
Chen, Ying-Hwa;Hung, Szu-Chun;Tarng, Der-Cherng
通讯作者：
Tarng, Der-Cherng