Loss of heterozygosity of selected tumor suppressor genes in human testicular germ cell tumors.

Human testicular germ cell tumors (TGCTs) are histologically heterogenous neoplasms with a variable malignant potential. Two main groups of germ cell tumors occur in men: seminomas and nonseminomas. In the present study, a set of four tumor suppressor genes was investigated in testicular cancers. CDH1, APC, p53, and nm23-H1 genes were tested for loss of heterozygosity (LOH). Thirty-eight testicular germ cell tumors (17 seminomas and 21 nonseminomas) were analyzed by PCR using restriction fragment length polymorphism or the dinucleotide/tetranucleotide repeat polymorphism method. An allelic loss of p53 at exon 4 was detected in five nonseminomas, whereas LOH of p53 at intron 6 occurred in one of the seminoma and two of the nonseminoma samples. Allelic losses of the APC gene were present in three seminomas and one nonseminoma, whereas one seminoma and three nonseminomas showed LOH of CDH1. The analysis of allelic losses showed no common structural genetic alterations in tumor tissues, although a different pattern of LOH was observed between the two main histological groups of TGCTs.

Multidrug efflux transporters limit accumulation of inorganic, but not organic, mercury in sea urchin embryos.

Mercuric compounds are persistent global pollutants that accumulate in marine organisms and in humans who consume them. While the chemical cycles and speciation of mercury in the oceans are relatively well described, the cellular mechanisms that govern which forms of mercury accumulate in cells and why they persist are less understood. In this study we examined the role of multidrug efflux transport in the differential accumulation of inorganic (HgCl(2)) and organic (CH(3)HgCl) mercury in sea urchin (Strongylocentrotus purpuratus) embryos. We found that inhibition of MRP/ABCC-type transporters increases intracellular accumulation of inorganic mercury but had no effect on accumulation of organic mercury. Similarly, pharmacological inhibition of metal conjugating enzymes by ligands GST/GSH significantly increases this antimitotic potency of inorganic mercury, but had no effect on the potency of organic mercury. Our results point to MRP-mediated elimination of inorganic mercury conjugates as a cellular basis for differences in the accumulation and potency of the two major forms of mercury found in marine environments.

Toxicological characterization of the new water cleaning product and its waste by-product.

Water extracts genotoxicity of the coagulant produced from industrial waste (red mud and waste base) and its waste mud remained after waste water treatment by the coagulation/flocculation process were studied. Tests were conducted in order to confirm nontoxicity of this new product prior to commercial production and usage and also to recommend a safe way for a handling and disposal of the remaining waste material. The toxicity investigation included (i) determining frequency of the cell survival, (ii) the Ames assays, (iii) micronucleus assay, and (iv) cell proliferation kinetics (expressed as mitotic index). These techniques were also employed in toxicity testing of the different concentrations of metal salts, zinc chloride, and lead nitrate in this case since these two elements were present in high concentrations in the waste water intended for the purification with the new coagulant. Mixture of metal salts in the concentrations that represent maximum allowed values for water extracts of technological waste was also tested. Two strains of Salmonella typhimurium, TA98, and TA100 were used for determining cytotoxicity and for the Ames test, while the cytogenetic investigations were performed on human peripheral blood lymphocytes. Water extracts of the coagulant and its waste mud did not induce a significant increase of the micronuclei in human peripheral blood lymphocytes. They also did not disturb lymphocyte proliferation kinetics in vitro. As regards lead nitrate it proved not to be cytotoxic on bacterial strains in the tested concentration range (1-100 mg/L), whereas zinc chloride showed cytotoxic effect for the concentrations above 25 mg/L. The Ames test results for the noncytotoxic concentrations of these metals were negative. Comparing to the negative control a significantly higher number of the micronuclei was determined after the treatment of the whole blood with 100 mg/L of zinc chloride, as well as with 10 and 100 mg/L of lead nitrate. A linear, dose dependent increase was obtained for both salts. Similar results were obtained on the basis of the mitotic index.