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杨梅素、槲皮素、(+)-儿茶素和(-)-表儿茶素可保护人肝癌细胞免受N-亚硝胺诱导的DNA损伤。

Myricetin, quercetin, (+)-catechin and (-)-epicatechin protect against N-nitrosamines-induced DNA damage in human hepatoma cells.

作者信息

Delgado M E, Haza A I, García A, Morales P

机构信息

Departamento de Nutrición, Bromatología y Tecnología de los Alimentos, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain.

出版信息

Toxicol In Vitro. 2009 Oct;23(7):1292-7. doi: 10.1016/j.tiv.2009.07.022. Epub 2009 Jul 21.

Abstract

The aim of this study was to investigate the protective effect of myricetin, quercetin, (+)-catechin and (-)-epicatechin, against N-nitrosodibutylamine (NDBA) and N-nitrosopiperidine (NPIP)-induced DNA damage in human hepatoma cells (HepG2). DNA damage (strand breaks and oxidized purines/pyrimidines) was evaluated by the alkaline single-cell gel electrophoresis or Comet assay. (+)-Catechin at the lowest concentration (10 microM) showed the maximum reduction of DNA strand breaks (23%), the formation of endonuclease III (Endo III, 19-21%) and formamidopyrimidine-DNA glycosylase (Fpg, 28-40%) sensitive sites induced by NDBA or NPIP. (-)-Epicatechin also decreased DNA strand breaks (10 microM, 20%) and the oxidized pyrimidines/purines (33-39%) induced by NDBA or NPIP, respectively. DNA strand breaks induced by NDBA or NPIP were weakly reduced by myricetin at the lowest concentration (0.1 microM, 10-19%, respectively). Myricetin also reduced the oxidized purines (0.1 microM, 17%) and pyrimidines (0.1 microM, 15%) induced by NDBA, but not the oxidized pyrimidines induced by NPIP. Quercetin did not protect against NDBA-induced DNA damage, but it reduced the formation of Endo III and Fpg sensitive sites induced by NPIP (0.1 microM, 17-20%, respectively). In conclusion, our results indicate that (+)-catechin and (-)-epicatechin at the concentrations tested protect human derived cells against oxidative DNA damage effects of NDBA and NPIP. However, myricetin at the concentrations tested only protects human cells against oxidative DNA damage induced by NDBA and quercetin against oxidative DNA damage induced by NPIP.

摘要

本研究旨在探讨杨梅素、槲皮素、(+)-儿茶素和(-)-表儿茶素对N-亚硝基二丁胺(NDBA)和N-亚硝基哌啶(NPIP)诱导的人肝癌细胞(HepG2)DNA损伤的保护作用。通过碱性单细胞凝胶电泳或彗星试验评估DNA损伤(链断裂和氧化嘌呤/嘧啶)。最低浓度(10微摩尔)的(+)-儿茶素显示出DNA链断裂减少最多(23%),由NDBA或NPIP诱导的核酸内切酶III(Endo III,19 - 21%)和甲酰胺嘧啶-DNA糖基化酶(Fpg,28 - 40%)敏感位点的形成减少。(-)-表儿茶素也分别减少了由NDBA或NPIP诱导的DNA链断裂(10微摩尔,20%)和氧化嘧啶/嘌呤(33 - 39%)。最低浓度(0.1微摩尔)的杨梅素对由NDBA或NPIP诱导的DNA链断裂的减少作用较弱(分别为10 - 19%)。杨梅素还减少了由NDBA诱导的氧化嘌呤(0.1微摩尔,17%)和嘧啶(0.1微摩尔,15%),但未减少由NPIP诱导的氧化嘧啶。槲皮素不能保护细胞免受NDBA诱导的DNA损伤,但它减少了由NPIP诱导的Endo III和Fpg敏感位点的形成(0.1微摩尔,分别为17 - 20%)。总之,我们的结果表明,在所测试的浓度下,(+)-儿茶素和(-)-表儿茶素可保护人源细胞免受NDBA和NPIP的氧化DNA损伤作用。然而,在所测试的浓度下,杨梅素仅保护人细胞免受NDBA诱导的氧化DNA损伤,而槲皮素仅保护人细胞免受NPIP诱导的氧化DNA损伤。

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