In mammals, cadmium is widely considered as a non-genotoxic carcinogen acting through a methylation-dependent epigenetic mechanism. Here, the effects of Cd treatment on the DNA methylation patten are examined together with its effect on chromatin reconfiguration in Posidonia oceanica. DNA methylation level and pattern were analysed in actively growing organs, under short- (6 h) and long- (2 d or 4 d) term and low (10 mM) and high (50 mM) doses of Cd, through a Methylation-Sensitive Amplification Polymorphism technique and an immunocytological approach, respectively. The expression of one member of the CHROMOMETHYLASE (CMT) family, a DNA methyltransferase, was also assessed by qRT-PCR. Nuclear chromatin ultrastructure was investigated by transmission electron microscopy. Cd treatment induced a DNA hypermethylation, as well as an up-regulation of CMT, indicating that de novo methylation did indeed occur. Moreover, a high dose of Cd led to a progressive heterochromatinization of interphase nuclei and apoptotic figures were also observed after long-term treatment. The data demonstrate that Cd perturbs the DNA methylation status through the involvement of a specific methyltransferase. Such changes are linked to nuclear chromatin reconfiguration likely to establish a new balance of expressed/repressed chromatin. Overall, the data show an epigenetic basis to the mechanism underlying Cd toxicity in plants.

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In Posidonia oceanica cadmium induces changes in DNA methylation and chromatin patterning

Collectively, results from epidemiologic studies, laboratory bioassays, and human clinical intervention trials clearly support a protective role of selenium against cancer development. Several hypotheses have been proposed to explain these observations. Increased genomic instability, either inherent or induced by exogenous agents (mutagens or carcinogens), has been considered as a primary event leading to neoplastic transformation. This report deals specifically with the evidence for a role of selenium in the inhibition of carcinogen-induced covalent DNA adduct formation and retardation of oxidative damage to DNA, lipids and proteins, and for modulating cellular and molecular events that are critical in cell growth inhibition and in the multi-step carcinogenesis process. At present, the bulk of our knowledge on the role of selenium on genetic stability is based primarily on animal data and from studies conducted in in vitro systems. Studies performed in vitro showed that the dose and form of selenium compounds are critical factors with regard to cellular responses. Inorganic (at doses up to 10microM) and organic selenium compounds (at doses equal to or greater than 10microM) elicit distinctly different cellular responses. The recommended daily allowance (RDA) is 50-70 microgramSe per day for healthy adults; with 40 microgramSe as minimum requirement. Less than 11 microgramSe will definitely put people at risk of deficiency that would be expected to cause genetic damage. Daily doses of 100-200 microgramSe inhibited genetic damage and cancer development in humans. About 400 microgramSe per day is considered an upper limit. Clearly, doses above the RDA are needed to inhibit genetic damage and cancer. However, it has been hypothesized that the intake of excessive doses of selenium may cause oxidative damage, leading to genomic instability. The use of a cocktail consisting of selenium, and other vitamins and minerals appears to be a promising approach to inhibit genetic damage and the development of cancer. It is the author's recommendation that development of mechanism-based hypotheses that can be tested in pilot studies in different populations prior to a large-scale clinical trial in humans, is of paramount importance in order to better understand the role of selenium on genetic stability and cancer.

The protective role of selenium on genetic damage and on cancer

Cadmium (Cd) is one of the most toxic environmental pollutants affecting cytogenetically the various organisms. The cytogenetic damage in root tip cells exposed to cadmium nitrate (CdNO3) solutions at four different concentrations (1, 10, 100 and 200 microM) was evaluated with biological tests based on micronucleus (MN) assay in two plant species, Allium sativum and Vicia faba. Additionally to the cytogenetic analysis, lipid peroxidation analyses were performed in both A.sativum and V.faba roots. Cd enhanced the MN frequency in both A.sativum and V.faba root tip cells, but no dose-dependent. Induction of MN is not depending on CdNO3 concentrations. Besides, high concentrations of Cd decreased the mitotic index and caused the delay in mitosis stages in both plants, mainly in V.faba. On the other hand, lipid peroxidation was significantly enhanced with external Cd in V.faba. The results clearly indicate that high concentrations of cadmium induce the lipid peroxidation resulting in oxidative stress that may contribute to the genotoxicity and cytotoxicity of Cd ions.

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Cadmium-induced genotoxicity, cytotoxicity and lipid peroxidation in Allium sativum and Vicia faba

Effects of Se and Zn supplementation on the antagonism against Pb and Cd in vegetables.

Effects of cadmium on meristem activity and nucleus ploidy in roots of Pisum sativum L. cv. Frisson seedlings

The antagonistic effect of calcium (Ca2+), zinc (Zn2+) and selenium (Se4+) at different concentrations (10-2-10-6 M) against cadmium (Cd2+) induced genotoxic effects in root cells of Hordeum vulgare were studied. The results showed that 10-3-10-5 M could induce chromosomal aberrations and micronuclei formation. But in the treatment with 10-2-10-6 M of Ca2+, Zn2+ and Se4+ together with Cd2+ (10-3-10-5 M), respectively, the frequencies of chromosomal aberrations and micronuclei effectively decreased after 48 h of treatment. The treatment with 10-4-10-6 M of Ca2+ together with 10-4-10-5 M Cd2+, 10-6 M of Zn2+ together with 10-5 M Cd2+ and 10-6 M of Se4+ together with 10-5 M Cd2+ suggested rather obvious antagonistic effects. The order of the antagonisms of Ca2+, Se4+ and Zn2+ against Cd2+ toxicity was Ca2+>Se4+>Zn2+. The degree of antagonisms of Ca2+, Se4+ and Zn2+ against Cd2+ related to their concentration ratio.

Hong Xiao

Papers

Antagonistic effect of calcium, zinc and selenium against cadmium induced chromosomal aberrations and micronuclei in root cells of Hordeum vulgare