Fumonisin B1 Epigenetically Regulates PTEN Expression and Modulates DNA Damage Checkpoint Regulation in HepG2 Liver Cells

Fumonisin B1 (FB1), a Fusarium-produced mycotoxin, is found in various foods and feeds. It is a well-known liver carcinogen in experimental animals; however, its role in genotoxicity is controversial. The current study investigated FB1-triggered changes in the epigenetic regulation of PTEN and determined its effect on DNA damage checkpoint regulation in human liver hepatoma G2 (HepG2) cells. Following treatment with FB1 (IC50: 200 µM; 24 h), the expression of miR-30c, KDM5B, PTEN, H3K4me3, PI3K, AKT, p-ser473-AKT, CHK1, and p-ser280-CHK1 was measured using qPCR and/or Western blot. H3K4me3 enrichment at the PTEN promoter region was assayed via a ChIP assay and DNA damage was determined using an ELISA. FB1 induced oxidative DNA damage. Total KDM5B expression was reduced, which subsequently increased the total H3K4me3 and the enrichment of H3K4me3 at PTEN promoters. Increased H3K4me3 induced an increase in PTEN transcript levels. However, miR-30c inhibited PTEN translation. Thus, PI3K/AKT signaling was activated, inhibiting CHK1 activity via phosphorylation of its serine 280 residue preventing the repair of damaged DNA. In conclusion, FB1 epigenetically modulates the PTEN/PI3K/AKT signaling cascade, preventing DNA damage checkpoint regulation, and induces significant DNA damage.

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Comparison of hepatotoxicity and mechanisms induced by triclosan (TCS) and methyl-triclosan (MTCS) in human liver hepatocellular HepG2 cells

Toxicology Research ◽

10.1039/c8tx00199e ◽

2019 ◽

Vol 8 (1) ◽

pp. 38-45 ◽

Cited By ~ 8

Author(s):

Lu Wang ◽

Boyu Mao ◽

Huixin He ◽

Yu Shang ◽

Yufang Zhong ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Hepg2 Cells ◽

Human Liver ◽

Oxidative Dna Damage ◽

Repair Process ◽

Signal Pathways ◽

Cycle Arrest ◽

Damage Repair ◽

Methyl Triclosan

TCS and MTCS could induce oxidative DNA damage, apoptosis, and cell cycle arrest and initiate the DNA damage repair process by regulating different signal pathways.

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The Effect of Ellagic Acid on Paraoxanase - 1 Activity and DNA Damage in Acute Exercise

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2019/v29i530250 ◽

2019 ◽

pp. 1-7

Author(s):

Ersan Kara ◽

Funda Karabağ Çoban ◽

Mustafa Akıl ◽

Recep Liman ◽

İbrahim Hakkı Ciğerci

Keyword(s):

Dna Damage ◽

Ellagic Acid ◽

Oxidative Dna Damage ◽

Acute Exercise ◽

Paraoxonase 1 ◽

Assay Method ◽

Control Group ◽

Control Groups ◽

Experimental Animals

The purpose of this study was to evaluate the correlation between exhaustive and intensive exercise with changes in paraoxonase-1 enzyme activity, oxidative DNA damage and the role of ellagic acid against possible damage. The study was carried out on 32 male and adult Spraque - Dawley rats at the Experimental Animal Research and Research Center of Afyon Kocatepe University. The experimental animals were equally divided into four groups. Swimming exercises were performed as acute exercises for once and experimental animals are made to swim in groups including two rats following the completion of the study and before the decapitation. At the end of the experiment, obtained blood samples; Paraoxonase-1 (PON-1), Malondialdehyde (MDA) and 8-HydroxyGuanine (8-OhdG) levels were measured to determine DNA damage and DNA damage was assessed by Comet Assay method. As a result, PON-1 levels in rats with intense swimming training were found to be significantly lower (p <0.05) than the control group. MDA and (8-OhdG) levels were significantly higher in the swimming group than in the control group (p <0.05). As to the DNA damage determination by COMET analysis, DNA damage was observed in the swimming groups according to the control groups. When the ellagic acid groups were compared with the swimming groups, there was a significant increase in PON-1 levels, and the levels of MDA and (8-OhdG) were significantly lower than the swimming groups. The DNA damage was also found to be low in these groups.

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Verbesina encelioides: cytotoxicity, cell cycle arrest, and oxidative DNA damage in human liver cancer (HepG2) cell line

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-016-1106-0 ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 5

Author(s):

Mai M. Al-Oqail ◽

Maqsood A. Siddiqui ◽

Ebtesam S. Al-Sheddi ◽

Quaiser Saquib ◽

Javed Musarrat ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Liver Cancer ◽

Cell Cycle Arrest ◽

Cell Line ◽

Human Liver ◽

Oxidative Dna Damage ◽

Hepg2 Cell Line ◽

Cycle Arrest ◽

Human Liver Cancer

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Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2)

APOPTOSIS ◽

10.1007/s10495-012-0705-6 ◽

2012 ◽

Vol 17 (8) ◽

pp. 852-870 ◽

Cited By ~ 423

Author(s):

Vyom Sharma ◽

Diana Anderson ◽

Alok Dhawan

Keyword(s):

Dna Damage ◽

Zinc Oxide ◽

Zinc Oxide Nanoparticles ◽

Human Liver ◽

Oxidative Dna Damage ◽

Liver Cells ◽

Oxide Nanoparticles ◽

Human Liver Cells

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In situ detection of oxidative DNA damage, 8-hydroxydeoxyguanosine, in chronic human liver disease

Journal of Hepatology ◽

10.1016/s0168-8278(01)00171-4 ◽

2001 ◽

Vol 35 (5) ◽

pp. 613-618 ◽

Cited By ~ 71

Author(s):

Takuya Kitada ◽

Shuichi Seki ◽

Shuji Iwai ◽

Takao Yamada ◽

Hiroki Sakaguchi ◽

...

Keyword(s):

Dna Damage ◽

Liver Disease ◽

Human Liver ◽

Oxidative Dna Damage ◽

In Situ Detection ◽

Human Liver Disease

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Sterigmatocystin-induced oxidative DNA damage in human liver-derived cell line through lysosomal damage

Toxicology in Vitro ◽

10.1016/j.tiv.2014.08.007 ◽

2015 ◽

Vol 29 (1) ◽

pp. 1-7 ◽

Cited By ~ 33

Author(s):

Wei Gao ◽

Liping Jiang ◽

Lan Ge ◽

Min Chen ◽

Chengyan Geng ◽

...

Keyword(s):

Dna Damage ◽

Cell Line ◽

Human Liver ◽

Oxidative Dna Damage

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Early toxic effects of fumonisin B1 in rat liver

Human & Experimental Toxicology ◽

10.1177/0960327108100418 ◽

2008 ◽

Vol 27 (12) ◽

pp. 895-900 ◽

Cited By ~ 15

Author(s):

AM Domijan ◽

D Želježić ◽

M Peraica ◽

G Kovačević ◽

G Gregorović ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Wistar Rats ◽

Fumonisin B1 ◽

Tail Length ◽

Male Adult ◽

Experimental Animals ◽

Mitotic Figures ◽

And Control ◽

Higher Doses

Mycotoxin fumonisin B1 (FB1) is hepatotoxic and carcinogenic in experimental animals. It is known that long-term exposure of experimental animals to FB1 causes apoptosis and lipid peroxidation. In this study, male adult Wistar rats were treated with single FB1 doses (5, 50, and 500 μg/kg b.w.) and sacrificed 4, 24, and 48 hours after treatment. Parameters of oxidative stress, histopathological changes, and DNA damage were monitored in the liver of treated and control animals. Parameters of oxidative stress were not affected by such treatment. A significant increase in apoptotic cells appeared in animals when 5 μg/kg b.w. dose was given and sacrificed after 24 hours with further increase at higher doses. In contrast to the number of mitotic figures and karyomegaly seen mostly at lower FB1 doses, necrosis was the prominent feature at higher doses. Significant increase in liver cells DNA mobility was observed 48 hours following treatment with 50 and 500 μg/kg b.w. as compared to control (tail length 15.2 ± 0.3, 16.4 ± 0.5, and 13.5 ± 0.1 μm, respectively). Tail intensity appeared to be more sensitive parameter for detecting DNA damage even at 5 μg/kg b.w. after 48 hours (1.69 ± 0.27% DNA; control 0.59 ± 0.11% DNA). This study proved that FB1-induced DNA damage is time- and dose-dependent, and that it could be caused in Wistar rats by a single dose.

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