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Mercury is a major issue in environmental health, as it can be biotransformed to methylmercury, accumulate into aquatic organisms, and enter the food chain. Therefore, we searched for molecular markers for methylmercury exposure comparing, by differential display, exposed Xenopus embryos to controls. We found two genes whose expression is completely inhibited by CH3HgCl, and we propose them as biomarkers of exposure. The first transcript appears to be a novel gene, with a short region similar to the human iron-sulfur subunit of succinate dehydrogenase. The second gene presents a high similarity with the human homeodomain-interacting protein kinase 3 (HIPK3), a protein that is known to be involved in the apoptotic signaling pathway. These molecular biomarkers could be used to detect very early effects of the metal; furthermore, they could be useful in understanding the molecular mechanisms of mercury toxicity. [ABSTRACT FROM AUTHOR]

We used field-emission scanning electron microscopy (FESEM) coupled with energy dispersive X-ray spectroscopy (EDS) microanalysis to determine size, shape, and elemental composition of particles in the liver and kidney autopsy of 35 subjects living in Sardinia. Particles were detected in 94% of livers and in 97% of kidney samples as aggregates, ranging between 50 nm and 100 μm. A total of 513 particle aggregates were observed in all tissues (276 in the liver and 237 in the kidney samples). Aggregates consisted of single elements (As, Ba, Cu, F, Fe, Ge, Hg, Ni, P, Pb, S, Si, Ti) or multiple association of elements, up to six. Silicon and Fe were the main element constituents (presence in 61% and 23% of the total Pags) followed by Al, Hg, Ni, Pb, and Ti (< 1%). Calcium, Cl, Co, Cr, Na, K, P, Sc, Sn, W, V, Zn, sometimes Mg, Rh, and Ta, were also detected. Overall, our findings suggest that the ubiquitous presence of metal species as particle aggregates in human tissues would be a condition of normality, although such presence per se is far from being used as a toxicity biomarker. Before being able to clarify the implications of particles in diseases or normal physiological processes, the biological meaning of particles background level we observed in liver and kidney must be elucidated. [ABSTRACT FROM AUTHOR]

Abstract: The human wild type p53 gene, key for apoptosis, was introduced into the pheochromocytoma (PC12) cell line, to create a mechanistically-based in vitro test model for the detection of p53-mediated toxicity. Expression of the wt p53 gene was regulated by a system, which allowed or blocked expression p53 by absence or presence of tetracycline in the culture media. Western blot analyses confirmed an inducible and tetracycline-dependent expression of the wt p53 protein. Functionality of the p53 protein was verified by camptothecin treatment, known to induce p53-dependent apoptosis. Results showed that p53-expressing cells were significantly more sensitive to camptothecin induced cytotoxicity compared to non-expressing cells, and presented a significantly higher incidence of apoptosis. A screening study on 31 metal compounds, showed that the classified human carcinogens (NaAsO2, CdSO4 ·8H2O, Na2CrO4 ·4H2O, MnCl2, (NH4)2PtCl6) significantly increased cytotoxicity in p53-expressing cells compared to non-expressing cells, suggesting that their cytotoxicity was p53-mediated. Finally, acute and subchronic treatment with methyl mercury showed no significant differences in cytotoxicity and the percentage of apoptosis or necrosis between p53-expressing and non-expressing differentiated cells, suggesting that methyl mercury cytotoxicity was p53-independent. [Copyright &y& Elsevier]