Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemoprotective effect of hydroxytyrosol (HT) against Sudan I-induced genotoxicity was investigated in a human hepatoma cell line, HepG2. The comet assay and micronucleus (MN) assay were used to monitor genotoxicity. Intracellular reactive oxygen species (ROS) formation was measured using a fluorescent probe, 2,7-dichlorofluorescein diacetate (DCFH-DA). The levels of oxidative DNA damage and lipid peroxidation were estimated by immunocytochemistry analysis of 8-hydroxydeoxyguanosine (8-OHdG) and by measuring levels of thiobarbituric acid-reactive substances (TBARS), respectively. Intracellular glutathione (GSH) level was estimated by fluorometric methods. The results showed that HT significantly reduced the genotoxicity caused by Sudan I. Furthermore, HT ameliorated lipid pexidation as demonstrated by a reduction in TBARS formation and attenuated GSH depletion in a concentration-dependent manner. It was also found that HT reduced intracellular ROS formation and 8-OHdG level caused by Sudan I. These results strongly suggest that HT has significant protective ability against Sudan I-induced genotoxicity.
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PMID:Inhibition of Sudan I genotoxicity in human liver-derived HepG2 cells by the antioxidant hydroxytyrosol. 1829 12

Hydroquinone (HQ) is used as an antioxidant in rubber industry and as a developing agent in photography. HQ is also an intermediate in the manufacture of rubber, food antioxidant and monomer inhibitor. However, the mechanisms of the effects, in particular those related to its genotoxicity in humans, are not well understood. The aim of this study was to assess the genotoxic effects of HQ and to identify and clarify the mechanisms, using human hepatoma HepG2 cells. DNA strand breaks and DNA-protein crosslinks (DPC) were measured by the proteinase K-modified alkaline single cell gel electrophoresis (SCGE) assays. Using the SCGE assay, a significant dose-dependent increment in DNA migration was detected at concentrations of HQ (6.25-25 microM); but at the higher tested concentrations (50 microM), a reduction in the migration compared to the maximum migration at 25 microM was observed. Post-incubation with proteinase K significantly increased DNA migration in cells exposed to higher concentrations of HQ (50 microM). A significant increase of the frequency of micronuclei was found in the range from 12.5 to 50 microM in the micronucleus test (MNT). The data suggested that HQ caused DNA strand breaks, DPC and chromosome breaks. To elucidate the oxidative DNA damage mechanism, the 2,7-dichlorofluorescein diacetate (DCFH-DA) and o-phthalaldehyde (OPT) were chosen to monitor the levels of reactive oxygen species (ROS) and glutathione (GSH), respectively. The present study showed that HQ induced the increased levels of ROS and depletion of GSH in HepG2 cells, the doses being 25-50 and 6.25-50 microM, respectively. Moreover, HQ significantly caused 8-hydroxydeoxyguanosine (8-OHdG) formation in HepG2 cells at concentrations from 12.5 to 50 microM. All these results demonstrate that HQ exerts genotoxic effects in HepG2 cells, probably through DNA damage by oxidative stress. GSH, as a main intracellular antioxidant, is responsible for cellular defense against HQ-induced DNA damage.
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PMID:Hydroquinone-induced genotoxicity and oxidative DNA damage in HepG2 cells. 1835 59

The present study was designed to investigate the modulatory effects of black tea polyphenols (Polyphenon-B) on phase I and phase II xenobiotic-metabolizing enzymes and oxidative stress in a rat model of hepatocellular carcinoma (HCC). Liver tumours induced in male Sprague-Dawley rats by dietary administration of rho-dimethylaminoazobenzene (DAB) increased cytochrome P450 (total and CYP1A1, 1A2 and 2B isoforms), cytochrome b(5), cytochrome b(5) reductase, glutathione S-transferase (GST total and GST-P isoform) and gamma-glutamyltranspeptidase (GGT) with decrease in quinone reductase (QR). This was accompanied by enhanced lipid and protein oxidation and compromised antioxidant defences associated with increased expression of the oxidative stress markers 4-hydroxynonenal (4-HNE), anti-hexanoyl lysine (HEL), dibromotyrosine (DiBrY) and 8-hydroxy 2-deoxyguanosine (8-OHdG). Dietary administration of Polyphenon-B effectively suppressed DAB-induced hepatocarcinogenesis, as evidenced by reduced preneoplastic and neoplastic lesions, modulation of xenobiotic-metabolizing enzymes and amelioration of oxidative stress. Thus, it can be concluded that Polyphenon-B acts as an effective chemopreventive agent by modulating xenobiotic-metabolizing enzymes and mitigating oxidative stress in an in vivo model of hepatocarcinogenesis.
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PMID:Black tea polyphenols modulate xenobiotic-metabolizing enzymes, oxidative stress and adduct formation in a rat hepatocarcinogenesis model. 1898 86

The non-enzymatic repair of DNA oxidative damage can occur in a purely chemical system, but data show that it might also occur in cells. Human hepatoma cells (SMMC-7721) and human hepatocyte cells (LO2) were treated with 200microM H(2)O(2) for 30min to induce oxidative DNA damage quantified by amount of 8-OHdG and degree of DNA strand breaks, without inducing enzymatic repair. The dynamics of enzymatic repair activity quantified by unscheduled DNA synthesis, within 30min after removal of H(2)O(2) enzymatic repair mechanism has not been initiated. However, pre-incubation with low micromolar level polyphenols, quercetin or rutin can significantly attenuate DNA damage in both cell lines, indicating that the polyphenols did not work through an enzymatic mechanism. Unscheduled DNA synthesis after removal of H(2)O(2) was also markedly decreased by quercetin and rutin. Combined with our previous studies of fast reaction chemistry, the inhibitory effect of polyphenols have to be assigned to non-enzymatic repair mechanism rather than to enzymatic repair mechanism or antioxidant mechanism.
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PMID:In vivo non-enzymatic repair of DNA oxidative damage by polyphenols. 1937 12

To observe the alteration in the expression of DNA repair enzymes hOGG1 and hMYHalpha and the change in 8-OHdG levels in the HBx gene-transfected cells HepG2/HBx and to explore the mechanisms of the HBV-associated hepatocellular carcinoma, the gene-transfected cells HepG2/HBx which stably expressed HBx was established, and the effect of HBx on the cell cycle and proliferation of HepG2 was examined. By using the beta-actin as the interior control, real-time polymerase chain reaction (Real-time qPCR) was employed to quantitatively detect the expression of DNA repair enzymes hOGG1 and hMYHalpha in the HepG2/HBx, the control cells HepG2 and HepG2 transfected with pcDNA3.1 vector (HepG2/pDNA3.1). The 8-OHdG levels were determined by HPLC/ECD in the established gene-transfected cells HepG2/HBx and the control cells HepG2 and HepG2/pcDNA3.1. Our results showed that the expression of DNA repair enzyme hMYHalpha in the HepG2/HBx (0.021+/-0.007) was significantly lower than that of HepG2 (0.099+/-0.041) (P<0.05) and HepG2/pDNA3.1 (0.121+/-0.005) (P<0.05). However, the no significant differences existed in the expression of DNA repair enzyme hOGG1 among the three cell strains (P>0.05). The 8-OHdG level in the HepG2/HBx was significantly higher than that in HepG2 and HepG2/pcDNA3.1 (P<0.05). It is concluded that HBx gene may inhibit the expression of DNA repair enzyme hMYHalpha mRNA to impair the ability to repair the intracellular DNA oxidative damage, to increase the oxidative DNA-adduct 8-OHdG and to affect the nucleotide excision repair function, thus participate in the occurrence and development of hepatocellular carcinoma.
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PMID:The effects of HBx gene on the expression of DNA repair enzymes hOGG1 and hMYHalpha mRNA in HepG2 cells. 1939 2

The chemoprotective effect of hydroxytyrosol (HT) against acrylamide (AA)-induced cytotoxicity and DNA damage was investigated in a human hepatoma cell line, HepG2. The cytotoxicity was estimated by methyl thiazol tetrazolium bromide (MTT) assay. The comet assay was used to monitor DNA damage. The intracellular reactive oxygen species (ROS) formation and the level of oxidative DNA damage were estimated by using 2,7-dichlorofluorescein diacetate (DCFH-DA) as a fluorescent probe and by using immunocytochemistry analysis of 8-hydroxydeoxyguanosine (8-OHdG). Intracellular glutathione (GSH) level was estimated by fluorometric methods. The results showed that HT significantly reduced the cytotoxicity, DNA damage, intracellular ROS formation and 8-OHdG level caused by AA in a concentration-dependent manner. It was also found that HT concentration-dependently attenuated GSH depletion in HepG2 cells treated with 10mM AA. These findings suggest that HT has a strong protective ability against the cytotoxicity and DNA damage caused by AA.
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PMID:Protective effect of hydroxytyrosol against acrylamide-induced cytotoxicity and DNA damage in HepG2 cells. 1942 82

Olaquindox, a synthetic antimicrobial compound, is widely used in China as feed additive for growth promotion. However, it is a mutagen with its functional mechanism yet to be unclear. The purpose of this study was to investigate the genotoxic effects of olaquindox in human hepatoma G2 (HepG2) cells and to determine whether the oxidative DNA damage participated in the mechanism of olaquindox toxicity. The results of cell survival assay revealed that the HepG2 cells viabilities were significantly inhibited by olaquindox in a dose- and time-dependent manner. The cytokinesis-block micronucleus (CBMN) assay demonstrated a clear dose-response relationship between olaquindox treatments and micronucleus (MN) frequencies. Moreover, marked increases of DNA fragment migration were observed in the single cell gel electrophoresis (SCGE) assay. These data suggest that olaquindox treatment produced serious chromosome damage and DNA damage in HepG2 cells. To elucidate the possible oxidative DNA damage mechanism of olaquindox genotoxic activity, the levels of the intracellular reactive oxygen species (ROS) and the formation of 8-hydroxydeoxyguanosine (8-OHdG) were detected. The results showed that olaquindox induced the increased levels of ROS and 8-OHdG in HepG2 cells. Considering all the results, it is inferred that olaquindox exerts genotoxic effects in HepG2 cells probably through the ROS-induced oxidative DNA damage.
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PMID:Olaquindox-induced genotoxicity and oxidative DNA damage in human hepatoma G2 (HepG2) cells. 1948 61

Deoxynivalenol (DON) is a trichothecene mycotoxin and a cereals contamination, whose cytotoxicity has been shown in animals and various cells. However, with respect to the deoxynivalenol-induced DNA damage, especially in humans, are not well understood. The aim of this study was to assess the role of oxidative stress in deoxynivalenol-induced DNA damage, using human hepatoma HepG2 cells. Exposure of the cells to DON caused significant increase of DNA migration in comet assay at concentrations of 3.75-30 microM, which suggests that DON caused DNA strand breaks. To elucidate the role of antioxidation in those effects, DNA migration was monitored by pre-treatment with hydroxytyrosol (HT) as an antioxidant in comet assay. It was found that DNA migration with pre-treatment of HT was dramatically decreased. The DNA damage induced by DON was almost completely prevented. In order to clarify the underlying mechanisms, we evaluated the level of reactive oxygen species (ROS) production with the 2,7-dichlorofluorescein diacetate (DCFH-DA) assay. Significant increase in the level of ROS was observed in HepG2 cells at a higher concentration (60 microM). The involvement of lipid peroxidation in the DNA damage of DON was confirmed by using immunoperoxidase staining for 8-hydroxydeoxyguanosine (8-OHdG) and by measuring levels of thiobarbituric acid-reactive substances (TBARS), the doses being 7.5-60 microM and 3.75-15 microM, respectively. These results indicate that the DNA damage induced by DON in HepG2 cells is probably related to the oxidative stress.
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PMID:The role of oxidative stress in deoxynivalenol-induced DNA damage in HepG2 cells. 1948 9

Patulin (PAT) is a mycotoxin produced by certain species of Penicillium and Aspergillus. The aim of this study was to assess PAT-induced DNA damage and to clarify the mechanisms, using human hepatoma G2 (HepG2) cells. PAT caused significant increase of DNA migration in single cell gel electrophoresis assay. To elucidate the role of glutathione (GSH), the intracellular GSH level was modulated by pre-treatment with buthionine-(S, R)-sulfoximine, a specific GSH synthesis inhibitor. It was observed that PAT significantly induced DNA damage in GSH-depleted HepG2 cells at lower concentrations. PAT induced the increased levels of reactive oxygen species and depletion of GSH in HepG2 cells using 2,7-dichlorofluorescein diacetate and 0-phthalaldehyde, respectively. PAT significantly increased the levels of 8-hydroxydeoxyguanosine and thiobarbituric acid-reactive substances in HepG2 cells. Also, PAT-induced p53 protein accumulation was observed in HepG2 cells, suggesting that the activation of p53 appeared to have been a downstream response to the PAT-induced DNA damage. These results demonstrate that PAT causes DNA strand breaks in HepG2 cells, probably through oxidative stress. Both GSH, as a main intracellular antioxidant, and p53 protein are responsible for cellular defense against PAT-induced DNA damage.
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PMID:Patulin-induced oxidative DNA damage and p53 modulation in HepG2 cells. 1974 5

6-gingerol, a major component of ginger, has antioxidant, anti-apoptotic, and anti-inflammatory activities. However, some dietary phytochemicals possess pro-oxidant effects as well, and the risk of adverse effects is increased by raising the use of doses. The aim of this study was to assess the genotoxic effects of 6-gingerol and to clarify the mechanisms, using human hepatoma G2 (HepG2) cells. Exposure of the cells to 6-gingerol caused significant increase of DNA migration in comet assay, increase of micronuclei frequencies at high concentrations at 20-80 and 20-40 microM, respectively. These results indicate that 6-gingerol caused DNA strand breaks and chromosome damage. To further elucidate the underlying mechanisms, we tested lysosomal membrane stability, mitochondrial membrane potential, the intracellular generation of reactive oxygen species (ROS) and reduced glutathione (GSH). In addition, the level of oxidative DNA damage was evaluated by immunocytochemical analysis on 8-hydroxydeoxyguanosine (8-OHdG). Results showed that lysosomal membrane stability was reduced after treatment by 6-gingerol (20-80 microM) for 40 min, mitochondrial membrane potential decreased after treatment for 50 min, GSH and ROS levels were significantly increased after treatment for 60 min. These suggest 6-gingerol induces genotoxicity probably by oxidative stress; lysosomal and mitochondrial damage were observed in 6-gingerol-induced toxicity.
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PMID:Genotoxic effect of 6-gingerol on human hepatoma G2 cells. 2016 13


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