DNA damage and metallothionein synthesis in human hepatoma cells (HepG2) exposed to cadmium

Fatur, T; Tušek, M; Falnoga, Ingrid; Ščančar, Janez; Lah, Tamara T.; Filipič, Metka

doi:10.1016/s0278-6915(02)00058-3

Cited by 54 publications

(24 citation statements)

References 28 publications

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“…Significant differences were observed between the untreated cells and those treated with 60 and 80 μM of cadmium. These results support previous studies showing induction of DNA damage in cadmium-treated human lung fibroblasts and HEPG2 cells (Fatur et al, 2002;Mouron et al, 2004).…”

Section: Induction Of Dna Damage By Cadmiumsupporting

confidence: 93%

p53-dependent but ATM-independent inhibition of DNA synthesis and G2 arrest in cadmium-treated human fibroblasts

Cao

Zhou

Simpson

et al. 2007

Toxicology and Applied Pharmacology

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This study focused on the activation of cell cycle checkpoint responses in diploid human fibroblasts that were treated with cadmium chloride and the potential roles of ATM and p53 signaling pathways in cadmium-induced responses. The alkaline comet assay indicated that cadmium caused a dosedependent increase in DNA damage. Cells that were rendered p53-defective by expression of a dominant-negative p53 allele or knockdown of p53 mRNA were more resistant to cadmium-induced inactivation of colony formation than normal and ataxia telangiectasia (AT) cells. Synchronized fibroblasts in S were more sensitive to cadmium toxicity than cells in G1 suggesting that cadmium may target some element of DNA replication. Cadmium produced a dose-and time-dependent inhibition of DNA synthesis. An immediate inhibition was associated with severe delay in progression through S phase and a delayed inhibition seen 24 h after treatment was associated with accumulation of cells in G2. AT and normal cells displayed similar patterns of inhibition of DNA synthesis and G2 delay after treatment with cadmium, while p53-defective cells displayed significantly less of the delayed inhibition of DNA synthesis and accumulation in G2 post-treatment. Total p53 protein and ser15-phosphorylated p53 were induced by cadmium in normal and AT cells. The p53 transactivation target Gadd45α was induced in both p53-effective and p53-defective cells after 4 h cadmium treatment, and this was associated with an acute inhibition of mitosis. Cadmium produced a very unusual pattern of toxicity in human fibroblasts, inhibiting DNA replication and inducing p53-dependent growth arrest but without induction of p21 Cip1/Waf1 or activation of Chk1.

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Section: Induction Of Dna Damage By Cadmiumsupporting

confidence: 93%

p53-dependent but ATM-independent inhibition of DNA synthesis and G2 arrest in cadmium-treated human fibroblasts

Cao

Zhou

Simpson

et al. 2007

Toxicology and Applied Pharmacology

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“…As expected, MTs synthesis was time dependent ( Figure 3), but in comparison with the human hepatoma cell line HepG2 checked previously (Fatur et al 2002), the induction process in astrocytoma-glioblastoma U87 MG proceeds slower. While in hepatoma cells the highest Cd and Zn binding on MTs was reached after 12 hours (Fatur et al 2002), in astrocytoma-glioblastoma cells the highest concentrations were not observed before 48 hours.…”

Section: Discussionsupporting

confidence: 81%

“…While in hepatoma cells the highest Cd and Zn binding on MTs was reached after 12 hours (Fatur et al 2002), in astrocytoma-glioblastoma cells the highest concentrations were not observed before 48 hours. But we cannot conclude that this was a plateau (the maximal concentration).…”

Section: Discussionmentioning

confidence: 81%

Metal binding of metallothioneins in human astrocytomas (U87 MG, IPDDC-2A)

et al. 2006

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Astroglia cells structurally and nutritionally support neurons in the central nervous system. They play an important role in guiding the construction of the nervous system and controlling the chemical and ionic environment of neurons. They also represent the major sites for accumulation and immobilisation of toxic metal ions most probably connected with metallothioneins. For this reason astroglia cells possess high cytosolic levels of metallothioneins I, II and III (MT-I,II,III). Our aim was to establish the inducibility and metal binding of MTs in two human astrocytoma cell lines, U87 MG (astrocytoma-glioblastoma, grade IV) and IPDDC-2A (astrocytoma, grade II), on exposure to cadmium chloride (1 microM). MTs were identified by molecular weight (size exclusion chromatography) and their metal content (Cd, Zn and Cu) to follow the interactions between metals. We showed that MTs are constitutively expressed in both human astrocytoma cell lines. In accordance with the higher malignancy grade of U87 MG, the amount of MTs was higher in U87 MG than in IPDDC-2A cells. After 24 hours of exposure to Cd their expression greatly increased in both cell lines and they were capable of immobilising almost all water soluble Cd. Induction of MTs in U87 MG cells was additionally followed up to 48 hours with exposure to different concentrations of CdCl(2) (1, 10 microM). Induction was a time dependent process throughout the period. Isoform III (identified by chromatographic separation of isoform III from I/II) was present at all exposure times, but only in traces with respect to the prevailing amounts of MT-I/II isoforms. So induction can be attributed to isoform I/II only.

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“…concentrations both for plant and animal tissues. Mitodepressive, turbogenic and cytotoxic effects of heavy metals were described for many plants (Wierzbicka 1999;Liu et al 2003;Glińska et al 2007) and animals (Bagchi et al 2002;Fatur et al 2002;Palus et al 2003). Data from literature confirm that inhibitory effect of Cu 2?…”

Section: Discussionmentioning

confidence: 81%

Red cabbage anthocyanin extract alleviates copper-induced cytological disturbances in plant meristematic tissue and human lymphocytes

2009

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Red cabbage is a source of health beneficial substances with antioxidant and antigenotoxic properties. HPLC analysis specifying the content of the investigated extract indicated that mainly anthocyanins (ATH) were responsible for its abilities. Cytological research was conducted with two experimental models: plant tissues--meristematic cells of Vicia faba, and animal tissue elements--human lymphocytes. Positive influence of ATH extract on mitotic activity of Vicia cells exposed to Cu(2+) stress, and inhibitory effect of ATH on cytotoxic actions of Cu(2+) on lymphocytes were demonstrated. In all experimental series with ATH application in combinations with Cu(2+), mitotic index (MI) were higher than those obtained for only Cu(2+) stressed tissues. Preincubation in ATH before Cu(2+) stress had the best effect. Similarly, after ATH applications in all tested series decrease in frequency of micronuclei (MN) appearance was noticed in comparison with only Cu(2+) stressed material. In the case of Vicia cells ATH acted effectively even applied after Cu(2+) stress. It suggests that this ATH mixture not only prevents and limits but also heals the cytological injury caused by Cu(2+) stress.

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DNA damage and metallothionein synthesis in human hepatoma cells (HepG2) exposed to cadmium

Cited by 54 publications

References 28 publications

p53-dependent but ATM-independent inhibition of DNA synthesis and G2 arrest in cadmium-treated human fibroblasts

p53-dependent but ATM-independent inhibition of DNA synthesis and G2 arrest in cadmium-treated human fibroblasts

Metal binding of metallothioneins in human astrocytomas (U87 MG, IPDDC-2A)

Red cabbage anthocyanin extract alleviates copper-induced cytological disturbances in plant meristematic tissue and human lymphocytes

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