Abstract:
BACKGROUND:Dietary polyphenols have been reported to have a variety of biological actions, including anticarcinogenic and antioxidant activities. AIM OF THE STUDY:In the present study we investigated the protective effect of dietary polyphenols against N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR) and benzo(a)pyrene (BaP)-induced DNA damage (strand breaks and oxidized purines/pyrimidines) in HepG2 cells. METHODS:Human hepatocellular carcinoma (HepG2) cells, which retain many specialized liver functions and drug metabolizing enzyme activities, were used as in vitro model for human hepatocytes. NDMA, NPYR and BaP were employed to induce DNA damage. DNA damage (strand breaks, oxidized pyrimidines and oxidized purines) was evaluated by the alkaline single cell gel electrophoresis or comet assay. RESULTS:None of the polyphenols concentrations tested in presence or absence of Fpg (formamidopyrimidine-DNA glycosylase), or Endo III (Endonuclease III) caused DNA damage per se. Increasing concentrations of BaP (25-100 microM) induced a significant increase of DNA strand breaks, Fpg and Endo III sensitive sites in a dose dependent manner. Myricetin and quercetin decreased DNA strand breaks and oxidized pyrimidines induced by NDMA, but not oxidized purines. However, both flavonoids reduced oxidized pyrimidines and purines induced by NPYR. DNA strand breaks induced by NPYR were prevented by quercetin, but not by myricetin. BaP-induced DNA strand breaks and oxidized pyrimidines were strongly reduced by myricetin and quercetin, respectively. While oxidized purines induced by BaP were reduced by quercetin, myricetin had no protective effect. (+)-Catechin and (-)-epicatechin reduced DNA strand breaks, oxidized pyrimidines and oxidized purines induced by NDMA. DNA strand breaks, and oxidized purines induced by NPYR were also prevented by (+)-catechin and (-)-epicatechin, while the maximum reduction of oxidized pyrimidines was found by (+)-catechin and (-)-epicatechin at 10 microM. (+)-Catechin and (-)-epicatechin decreased also DNA strand breaks and oxidized pyrimidines but not oxidized purines induced by BaP. CONCLUSIONS:Our results clearly indicate that polyphenols protect human derived cells against DNA strand breaks and oxidative DNA damage effects of NDMA, NPYR or BaP, three carcinogenic compounds which occur in the environment.
journal_name
Eur J Nutrjournal_title
European journal of nutritionauthors
Delgado ME,Haza AI,Arranz N,García A,Morales Pdoi
10.1007/s00394-008-0751-6subject
Has Abstractpub_date
2008-12-01 00:00:00pages
479-90issue
8eissn
1436-6207issn
1436-6215journal_volume
47pub_type
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journal_title:European journal of nutrition
pub_type: 杂志文章
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pub_type: 临床试验,杂志文章,随机对照试验
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