Correction: Association of GST Genetic Polymorphisms with the Susceptibility to Hepatocellular Carcinoma (HCC) in Chinese Population Evaluated by an Updated Systematic Meta-Analysis

BACKGROUND: Due to the possible involvement of Glutathione S-transferase Mu-1 (GSTM1) and Glutathione S-transferase theta-1 (GSTT1) in the detoxification of environmental carcinogens, environmental toxins, and oxidative stress products, genetic polymorphisms of these two genes may play important roles in the susceptibility of human being to hepatocellular carcinoma. However, the existing research results are not conclusive. METHODS: A systematic literature search using databases (PubMed, Scopus, Embase, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, Wanfang Data, etc.) for the eligible studies meeting the inclusion criteria including case-control studies or cohort studies is evaluated using an updated systematic meta-analysis. RESULTS: Significant increase in the risk of HCC in the Chinese population is found in GSTM1 null genotype (OR = 1.47, 95% CI: 1.21 to 1.79, P<0.001) and GSTT1 null genotype (OR = 1.38, 95% CI: 1.14 to 1.65, P<0.001). Analysis using the random-effects model found an increased risk of HCC in GSTM1-GSTT1 dual null population (OR = 1.79, 95% CI: 1.26 to 2.53, P<0.001). In addition, subgroup analyses showed a significant increase in the association of GST genetic polymorphisms (GSTM1, GSTT1, and GSTM1-GSTT1) with HCC in southeast and central China mainland. However, available data collected by this study fail to show an association between GST genetic polymorphisms and HCC in people from the Taiwan region (for GSTM1: OR = 0.78, 95% CI: 0.60 to 1.01, P = 0.06; for GSTT1: OR = 0.94, 95% CI: 0.78 to 1.14, P = 0.546; for GSTM1-GSTT1: OR = 1.04, 95% CI: 0.81 to 1.32, P = 0.77). Sensitivity analysis and publication bias diagnostics confirmed the reliability and stability of this meta-analysis. CONCLUSIONS: Our results indicate that both GSTM1 and GSTT1 null genotypes are associated with an increased HCC risk in Chinese population. Peoples with dual null genotypes of GSTM1-GSTT1 are more susceptible to developing HCC. In conclusion, GST genetic polymorphisms play vital roles in the development of HCC in the Chinese population

Acute toxicity of intravenously administered titanium dioxide nanoparticles in mice.

BACKGROUND: With a wide range of applications, titanium dioxide (TiO₂) nanoparticles (NPs) are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO₂ nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. METHODS: In this study, mice were injected intravenously with a single dose of TiO₂ NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg). Animal mortality, blood biochemistry, hematology, genotoxicity and histopathology were investigated 14 days after treatment. RESULTS: Death of mice in the highest dose (1387 mg/kg) group was observed at day two after TiO₂ NPs injection. At day 7, acute toxicity symptoms, such as decreased physical activity and decreased intake of food and water, were observed in the highest dose group. Hematological analysis and the micronucleus test showed no significant acute hematological or genetic toxicity except an increase in the white blood cell (WBC) count among mice 645 mg/kg dose group. However, the spleen of the mice showed significantly higher tissue weight/body weight (BW) coefficients, and lower liver and kidney coefficients in the TiO₂ NPs treated mice compared to control. The biochemical parameters and histological tissue sections indicated that TiO₂ NPs treatment could induce different degrees of damage in the brain, lung, spleen, liver and kidneys. However, no pathological effects were observed in the heart in TiO₂ NPs treated mice. CONCLUSIONS: Intravenous injection of TiO₂ NPs at high doses in mice could cause acute toxicity effects in the brain, lung, spleen, liver, and kidney. No significant hematological or genetic toxicity was observed

Metallic nickel nanoparticles may exhibit higher carcinogenic potential than fine particles in JB6 cells.

While numerous studies have described the pathogenic and carcinogenic effects of nickel compounds, little has been done on the biological effects of metallic nickel. Moreover, the carcinogenetic potential of metallic nickel nanoparticles is unknown. Activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) have been shown to play pivotal roles in tumor initiation, promotion, and progression. Mutation of the p53 tumor suppressor gene is considered to be one of the steps leading to the neoplastic state. The present study examines effects of metallic nickel fine and nanoparticles on tumor promoter or suppressor gene expressions as well as on cell transformation in JB6 cells. Our results demonstrate that metallic nickel nanoparticles caused higher activation of AP-1 and NF-κB, and a greater decrease of p53 transcription activity than fine particles. Western blot indicates that metallic nickel nanoparticles induced a higher level of protein expressions for R-Ras, c-myc, C-Jun, p65, and p50 in a time-dependent manner. In addition, both metallic nickel nano- and fine particles increased anchorage-independent colony formation in JB6 P+ cells in the soft agar assay. These results imply that metallic nickel fine and nanoparticles are both carcinogenetic in vitro in JB6 cells. Moreover, metallic nickel nanoparticles may exhibit higher carcinogenic potential, which suggests that precautionary measures should be taken in the use of nickel nanoparticles or its compounds in nanomedicine

Metallic nickel nanoparticles may exhibit higher carcinogenic potential than fine particles in JB6 cells.

While numerous studies have described the pathogenic and carcinogenic effects of nickel compounds, little has been done on the biological effects of metallic nickel. Moreover, the carcinogenetic potential of metallic nickel nanoparticles is unknown. Activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) have been shown to play pivotal roles in tumor initiation, promotion, and progression. Mutation of the p53 tumor suppressor gene is considered to be one of the steps leading to the neoplastic state. The present study examines effects of metallic nickel fine and nanoparticles on tumor promoter or suppressor gene expressions as well as on cell transformation in JB6 cells. Our results demonstrate that metallic nickel nanoparticles caused higher activation of AP-1 and NF-κB, and a greater decrease of p53 transcription activity than fine particles. Western blot indicates that metallic nickel nanoparticles induced a higher level of protein expressions for R-Ras, c-myc, C-Jun, p65, and p50 in a time-dependent manner. In addition, both metallic nickel nano- and fine particles increased anchorage-independent colony formation in JB6 P+ cells in the soft agar assay. These results imply that metallic nickel fine and nanoparticles are both carcinogenetic in vitro in JB6 cells. Moreover, metallic nickel nanoparticles may exhibit higher carcinogenic potential, which suggests that precautionary measures should be taken in the use of nickel nanoparticles or its compounds in nanomedicine

Subgroup analysis of ^$the adjusted association between <i>GSTM1-GSTT1</i> null genotype and HCC risk.

<p>M: model of meta-analysis; R: random-effects model; F: fixed-effects model. <i>P_H</i>: <i>P</i> value of heterogeneity test. <i>P_E</i>: <i>P</i> value of Egger’s test. <i>P_OR</i>: <i>P</i><0.001 replace the <i>P</i> = 0.000 and the <i>P</i> less than 0.001. ^$: adjusted association (after omitting 3 articles <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057043#pone.0057043-Bian2" target="_blank">[30]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057043#pone.0057043-Yu3" target="_blank">[37]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057043#pone.0057043-Deng1" target="_blank">[44]</a>).</p

Subgroup analysis of the association between <i>GSTM1</i> null genotype and HCC risk.

<p>M: model of meta-analysis; R: random-effects model; F: fixed-effects model. <i>P_H</i>: <i>P</i> value of heterogeneity test. <i>P_E</i>: <i>P</i> value of Egger’s test. <i>P_OR</i>: <i>P</i><0.001 replace <i>P</i> = 0.000 and <i>P</i> less than 0.001. @: <i>P</i> values could not be calculated.</p