The role of oxidative stress in Sudan IV-induced DNA damage in human liver-derived HepG2 cells.

Abstract:

OBJECTIVES:We evaluated the role of oxidative stress in Sudan IV-induced DNA damage, using human liver-derived HepG2 cells. METHODS:The DNA damaging effects of Sudan IV in HepG2 cells were evaluated by alkaline single cell gel electrophoresis assay and micronucleus test (MNT). To clarify the underlying mechanisms, we monitored the intracellular generation of reactive oxygen species (ROS) by 2, 7-dichlorofluorescein diacetate assay and the level of oxidative DNA damage by immunoperoxidase staining for 8-hydroxydeoxyguanosine (8-OHdG). Furthermore, the intracellular glutathione (GSH) level was moderated by pretreatment with buthionine-(S,R)-sulfoximine (BSO), a specific GSH synthesis inhibitor. RESULTS:A significant dose-dependent increment in DNA migration was detected at all tested concentrations (25-100 μM) of Sudan IV. And in the MNT, a significant increase of the frequency of micronuclei was found at higher tested concentrations (50-100 μM). The data suggested that Sudan IV caused DNA strand breaks and chromosome breaks. In addition, significantly increased levels of ROS, 8-OHdG formation were observed in HepG2 cells. It was also found that depletion of GSH in HepG2 cells with BSO dramatically increased the susceptibility of HepG2 cells to Sudan IV-induced DNA damage. CONCLUSIONS:Based on these data we believe that Sudan IV exerts toxic effects in HepG2 cells, probably through oxidative DNA damage induced by intracellular ROS and depletion of GSH.

journal_name

Environ Toxicol

journal_title

Environmental toxicology

authors

Zhang Y,An Y,Jiang L,Geng C,Cao J,Jiang L,Zhong L

doi

10.1002/tox.20558

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

292-9

issue

3

eissn

1520-4081

issn

1522-7278

journal_volume

26

pub_type

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