Long-term exposure to hexavalent chromium inhibits expression of tumor suppressor genes in cultured cells and in mice

Fan, Yunxia; Ovesen, Jerald L.; Puga, Alvaro

doi:10.1016/j.jtemb.2012.04.009

Cited by 21 publications

(6 citation statements)

References 29 publications

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“…In comparison with Saos-2, NHDFs showed upregulation in Bax and Bim genes, depending on the Cr content (without the addition of camptothecin). This finding is in accordance with the study by Fan et al (2012), in which mouse hepatoma Hepa-1 cells grown in the presence of 0.25 μmol/L K 2 CrO 4 for 5 passages upregulated the expression of Bax, Bid, Bak and BCL-2 (Fan et al, 2012). Moreover, in the current experiments, when camptothecin was added, the expression of Bax and Bim increased 4 times on PS.…”

Section: Apoptosissupporting

confidence: 93%

Effect of diamond-like carbon doped with chromium on cell differentiation, immune activation and apoptosis

Trávníčková¹,

Vandrovcová²,

Filová

et al. 2020

eCM

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Diamond-like carbon (DLC) is a biocompatible material that has many potential biomedical applications, including in orthopaedics. DLC layers doped with Cr at atomic percent (at.%) of 0, 0.9, 1.8, 7.3, and 7.7 at.% were evaluated with reference to their osteoinductivity with human bone marrow mesenchymal stromal cells (hMSCs), immune activation potential with RAW 264.7 macrophage-like cells, and their effect on apoptosis in Saos-2 human osteoblast-like cells and neonatal human dermal fibroblasts (NHDFs). At mRNA level, hMSCs on DLC doped with 0.9 and 7.7 at.% of Cr reached higher maximum values of both RUNX2 and alkaline phosphatase. An earlier onset of mRNA production of type I collagen and osteocalcin was also observed on these samples; they also supported the production of both type I collagen and osteocalcin. RAW 264.7 macrophages were screened using a RayBio™ Human Cytokine Array for cytokine production. 10 cytokines were at a concentration more than 2 × as high as the concentration of a positive control, but the values for the DLC samples were only moderately higher than the values on glass. NHDF cells, but not Saos-2 cells, had a higher expression of pro-apoptotic markers Bax and Bim and a lower expression of anti-apoptotic factor BCL-XL in proportion to the Cr content. Increased apoptosis was also proven by annexin V staining. These results show that a Cr-doped DLC layer with a lower Cr content can act as an osteoinductive material with relatively low immunogenicity, but that a higher Cr content can induce cell apoptosis.

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Section: Apoptosissupporting

confidence: 93%

Effect of diamond-like carbon doped with chromium on cell differentiation, immune activation and apoptosis

Trávníčková¹,

Vandrovcová²,

Filová

et al. 2020

eCM

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“…Recent findings in our laboratory have shown that both shortterm high-dose and long-term low-dose Cr(VI) exposure disrupt the inducible transcriptional response to B[a]P in Hepa-1 cells (Fan et al, 2012;Ovesen et al, 2014a;Wei et al, 2004). To determine whether these finding would also apply in vivo, we measure gene expression patterns in PSI, DSI, and liver of a battery of known or suspected B[a]P-target genes, including genes involved in drug metabolism (Cyp1a1 and Cyp1b1), oxidative stress (Hmox1, Nrf2, Gclc, Gclm, Gpx1, Gpx4, Gstp1, Gsta4, and Gstm5), tumor suppression (Cdkn1a/p21, Cdkn1b/p27, Cdkn2a/p16, Cdkn2b/p15, Cdkn2c/p18, Cdkn2c/p19, Hras, and P73), and inflammation (Tnfa and Il6).…”

Section: Gene Expression Changes Induced By Coexposure To Cr(vi) and mentioning

confidence: 99%

“…In Hepa-1 cells, long-term treatment with low concentrations of Cr(VI) has a significant effect on gene expression regulation in the form of structural changes that open the chromatin domains surrounding the binding sites for various transcription factors (Fan et al, 2012;Ovesen et al, 2014b). In vivo, oral exposure to B[a]P and Cr(VI) trigger different gene expression patterns depending on the particular tissue studied.…”

Section: Fig 5 Gene Expression Heat Map For a Psimentioning

confidence: 99%

Long-term Coexposure to Hexavalent Chromium and B[a]P Causes Tissue-Specific Differential Biological Effects in Liver and Gastrointestinal Tract of Mice

et al. 2015

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Complex mixtures of environmental agents often cause mixture-specific health effects that cannot be accounted for by a single mechanism. To study the biological effects of exposure to a mixture of chromium-VI and benzo[a]pyrene (B[a]P), often found together in the environment, we exposed mice for 60 days to 0, 55, 550, or 5500 ppb Cr(VI) in drinking water followed by 90 days of coexposure to B[a]P at 0, 1.25, 12.5, or 125 mg/kg/day and examined liver and gastrointestinal (GI) tract for exposure effects. In the liver, the mixture caused more significant histopathology than expected from the sum of effects of the individual components, while in the GI tract, Cr(VI) alone caused significant enterocyte hypertrophy and increases in cell proliferation and DNA damage that were also observed in mice coexposed to B[a]P. Expression of genes involved in drug metabolism, tumor suppression, oxidative stress, and inflammation was altered in mixed exposures relative to control and to singly exposed mice. Drug metabolism and oxidative stress genes were upregulated and tumor suppressor and inflammation genes downregulated in the proximal GI tract, whereas most markers were upregulated in the distal GI tract and downregulated in the liver. Oral exposure to Cr(VI) and B[a]P mixtures appears to have tissue-specific differential consequences in liver and GI tract that cannot be predicted from the effects of each individual toxicant. Tissue specificity may be particularly critical in cases of extended exposure to mixtures of these agents, as may happen in the occupational setting or in areas where drinking water contains elevated levels of Cr(VI).

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“…It could cause proximal tubule injury that involves specific changes in cell-cell adhesion, cellular signaling pathways, and autophagic leading to cells' necrosis or apoptosis [58]. Overall, population exposure to mixtures of environmental toxicants, engages three major signaling pathways: (i) activation of detoxification genes; (ii) induction of signal transduction effectors; and (iii) epigenetic modification of chromatin marks [59].…”

Section: Other Heavy Metal Exposurementioning

confidence: 99%

The Impact of Pollution on Children’s Health: A Call for Global Accountability and Enforcement

Kharytonov¹

2013

Int. J. Child Health Nutr.

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Environmental pollution in large industrial centers has had a negative impact on the population's health, specifically among children. Our objective is to provide a systematic review of the literature, focusing on the impact of environmental pollutants from urban and metropolitan areas on pediatric health. Disregard for the Earth's atmosphere can negatively impact our fragile ecosystem and create a global toxicity. The impact of industrial growth and economic development has become paramount to modern society. Unfortunately, future generations will pay the consequences of the world's failure to implement regulations to secure a safe environment for our children's health and development. Pollutants penetrate an organism through different routes and change physiological processes, which leads to a decrease in microbial resistance by weakening the child's immune system. The major contaminants are: polycyclic aromatic hydrocarbons, lead, manganese, sulfur dioxide, airborne fine particles, and nitrogen dioxide. Xenobiotics negatively affect the morphological, functional, biochemical parameters, genetics, and epigenetics of the body. It is well documented that the physical development and psychological well-being of children is adversely affected by pollution. The accumulation of heavy metals and other contaminants adversely affected a child's health has been found in the pediatric population. An effort has been made to develop detoxicant remedies, in particular, some enterosorbents and natural adaptogens. Research is ongoing to improve medical rehabilitation of children, who already are affected. Public education and regulations regarding emerging non-pollutant industrial technologies is called for. A global system of accountability and enforcement regarding environmental protection needs to be implemented.

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Long-term exposure to hexavalent chromium inhibits expression of tumor suppressor genes in cultured cells and in mice

Cited by 21 publications

References 29 publications

Effect of diamond-like carbon doped with chromium on cell differentiation, immune activation and apoptosis

Effect of diamond-like carbon doped with chromium on cell differentiation, immune activation and apoptosis

Long-term Coexposure to Hexavalent Chromium and B[a]P Causes Tissue-Specific Differential Biological Effects in Liver and Gastrointestinal Tract of Mice

The Impact of Pollution on Children’s Health: A Call for Global Accountability and Enforcement

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