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Carcinogenic metals and NF-kappaB activation.

Epidemiological and animal studies suggest that several metals and metal-containing compounds are potent mutagens and carcinogens. These metals include chromium, arsenic, vanadium, and nickel. During the last two decades, chemical and cellular studies have contributed enormously to our understanding of the mechanisms of metal-induced pathophysiological processes. Although each of these metals is unique in its mechanism of action, some common signaling molecules, such as reactive oxygen species (ROS), may be shared by many of these carcinogenic metals. New techniques are now available to reveal the mechanisms of carcinogenesis in precise molecular terms. In this review, we focused our attentions on metal-induced signal transduction pathways leading to the activation of NF-kappaB, a transcription factor governing the expression of most early response genes involved in a number of human diseases.

Animals↗

Isolation, purification, and partial chemical characterization of chromium(III) fractions existing in brewer's yeast and Sabouraud's liquid medium.

An ethanol extract of brewer's yeast which had been cultivated in a medium containing trivalent 51Cr was analyzed for 51Cr compounds by using petroleum ether extraction, gel filtration, cation and anion exchange chromatography and thin layer chromatography. Similar analytical procedures as for the above analysis were used for studying 51Cr compounds formed in the spent culture medium and in a sterile medium. Several 51Cr fractions were isolated from the three chromium sources, but one anionic 51Cr fraction present in the yeast and in the spent culture medium was not found in the sterile medium. Molecular weight estimations of the 51Cr fractions by gel filtration chromatography showed that the 51Cr ion exchange fractions contained several 51Cr compounds. The molecular weights of these compounds ranged from 150 to 1000 daltons and the molecular weights of 51Cr compounds separated from the yeast were markedly lower than those of the corresponding ion exchange fractions isolated from the culture medium. By using thin layer chromatography it was possible to isolate 51Cr compounds from the main bulk of ninhydrin active impurities. The polarity of all 51Cr compounds was found to be greater than that of most amino acids. The 51Cr compounds isolated from the yeast were mixed with 125I-insulin and incubated, after which the solution was eluted through Sephadex G-50 gel to test if binding had occurred. Elution peaks of 51Cr and 125I-insulin showed that 51Cr compounds were not bound to the insulin.

Chromium↗

Seasonal variation of thallium, lead, and chromium concentrations in airborne particulate matter collected in an urban area.

In November 1985 a research program started, with the aim to evaluate seasonal variations in the concentrations of organic and inorganic pollutants in the atmosphere of Genoa. The program provided for the collection of samples of airborne particulate in five different areas with distinct urban characteristics. First results for chromium, lead, and thallium concentrations in an industrial and in an urban area are reported. Lead showed the highest concentration at both locations (geometric mean: 1.037 and 0.476 microgram/m3, respectively) and appeared to be little affected by seasonal variation. Private traffic was confirmed as the main source of this pollutant. Chromium and thallium geometric mean concentrations were 0.006 and 0.014 microgram/m3 in site A and 0.017 and 0.015 microgram/m3 in site B, respectively. In the urban location a good negative linear correlation was found between chromium and thallium concentration and mean ambient temperature; the domestic heating plants were suspected as important emission sources of these two compounds.

Air Pollutants↗

Reversible dimerization of C60 molecules in the crystal structure of the bis(arene)chromium fulleride [Cr(C7H8)]2C60.

Bis(toluene)chromium fulleride, [Cr(C(7)H(8))(2)]C(60), has been synthesized as a black microcrystalline powder from C(60) and [Cr(C(7)H(8))(2)] in toluene. [Cr(C(7)H(8))(2)]C(60) is an ionic compound in which the fullerene is negatively charged and the bis(toluene)chromium molecule positively charged. At T = 250 K a reversible first-order phase transition from a primitive cubic high-temperature phase to a triclinic low-temperature phase occurs. The high-temperature phase [Pm3 macro m, a = 9.9840 (1) A, T = 295 K] is composed of dynamically disordered fulleride anions and bis(toluene)chromium(I) cations in a CsCl-type arrangement. The triclinic low-temperature modification [P1 macro, a = 13.6414 (8), b = 13.8338 (7), c = 13.8548 (7) A, alpha = 91.830 (3), beta = 116.776 (2), gamma = 119.333 (2) degrees, T = 235 K] consists of ordered C(60) dimers and two crystallographically distinct bis(toluene)chromium entities.

Journal Article↗

Active oxygen species in DNA damage induced by carcinogenic metal compounds.

Some carcinogenic metal compounds [chromate(VI), Fe(III) nitrilotriacetate, cobalt(II), and nickel(II)[ induced formation of various oxygen radical species in the presence of hydrogen peroxide. These oxygen radicals were suggested to give different kinds of site-specific DNA damage; 8-hydroxyl-2'-deoxyguanosine formation is included in the DNA damage. Using pulsed-field gel electrophoresis, nickel sulfide was shown to induce oxidative DNA cleavage in cultured cells. On the basis of these findings, we have emphasized the role of oxygen radicals in metal carcinogenesis.

Amino Acid Sequence↗

Triorganotin-induced cytotoxicity to rat thymus, bone marrow and red blood cells as determined by several in vitro assays.

To further investigate the immunotoxic effects of tri-n-propyltin chloride (TPTC), tri-n-butyltin chloride (TBTC) and triphenyltin chloride (TPhTC) several cytotoxicity tests with a series of trialkyltin chlorides and TPhTC were carried out, using isolated rat thymocytes as target cells. Thymocytes, cultured in a serum-supplemented medium, were exposed to organotin concentrations ranging from 0.01 to 10 microM for periods up to 30 h. Parameters such as cell count, trypan blue exclusion, chromium release, thymidine incorporation and cyclic AMP production were used to evaluate the cytotoxicity of these compounds. The more lipophilic compounds TPTC, TBTC, tri-n-hexyltin chloride (THTC) and TPhTC appeared most cytotoxic, reducing thymidine incorporation at concentrations as low as 0.05-1 microM. Membrane damage as determined by trypan blue exclusion and chromium release occurred at higher levels (1-10 microM). The water soluble homologue trimethyltin chloride (TMTC) was least effective in all test models. When phosphate-buffered saline supplemented with glucose was used as incubation medium, TBTC appeared more cytotoxic to thymocytes. Using this medium in 5-h incubations the cytotoxicity of TBTC to thymus, bone marrow and red blood cells was compared. Bone marrow cells were slightly less sensitive than thymocytes, while red cells were relatively resistant. In conclusion, of the triorganotin compounds especially the lipophilic homologues are cytotoxic in vitro.

Animals↗

Metabolic reduction of chromium, as related to its carcinogenic properties.

At variance with Cr(III), Cr(VI) compounds easily cross cell membranes and exert genotoxic effects. No metabolic oxidation of Cr(III) could be detected, whereas Cr(VI) reduction was observed in the presence of body fluids and subcellular fractions of various tissues from several animal species. The differential efficiency of this process may account for the selection of target tissues in Cr(VI) carcinogenesis. For instance, reduction by saliva and gastric juice may explain a lack of carcinogenicity by the oral route; reduction inside erythrocytes may explain a lack of carcinogenicity at a distance from administration sites; reduction by the epithelial-lining fluid of terminal airways and by alveolar macrophages may be consistent with the occurrence of thresholds in lung carcinogenesis. Liver preparations displayed the top efficiency in reducing Cr(VI), whereas skeletal muscle, i.e., a typical target in experimental Cr(VI) carcinogenesis, had no detectable activity. Bronchial tree and peripheral lung parenchyma preparations from almost 100 individuals reduced Cr(VI) to a variable extent. The efficiency of lung parenchyma and of isolated alveolar macrophages was enhanced in cigarette smokers. In rats, Cr(VI) reduction by lung preparations was significantly stimulated by the repeated i.t. instillation of Cr(VI) itself. Among the electron donors (chiefly GSH) and enzymatic mechanisms responsible for the intracellular Cr(VI) reduction, such as cytochrome P-450 reductase, glutathione reductase, and aldehyde oxidase, an important role can be ascribed to cytosolic DT diaphorase activity, usually catalyzing a 2-electron reduction.

Animals↗

XANES spectroscopy studies of Cr(VI) reduction by thiols in organosulfur compounds and humic substances.

The reduction of Cr(VI) by the thiol-containing compounds cysteine and glutathione and by reduced sulfur in humic substances was monitored with sulfur and chromium X-ray absorption near-edge structure (XANES) spectroscopy in chromium-contaminated soils. Reaction of humic acids with Cr(VI) resulted in a reduction of the peak area of thiols and an increase in the peak area of disulfides in the sulfur XANES spectra. Analysis of the sulfur XANES spectra in various systems indicates that the reduction of Cr(VI) by humic substances involves a thiol/disulfide redox couple analogous to that of the Cr(VI) reduction by the simple thiol-containing compounds cysteine and glutathione. A fraction of the hexavalent chromium present in industrially-contaminated soils was not reducible by thiols. Reduction of Cr(VI) to Cr(III) in soils by thiols has little effect on the pH of the system in contrast to the pH decrease resulting from reduction by Fe(II).

Carcinogens, Environmental↗

An international literature survey of "IARC Group I carcinogens" reported in mainstream cigarette smoke.

The International Agency for Research on Cancer (IARC) currently lists 44 individual chemical agents, 12 groups or mixtures of chemicals and 13 exposure circumstances as "Group 1 human carcinogens". A comprehensive search of the published literature revealed that nine of the 44 chemical agents classified as "Group I carcinogens" by IARC have been reported to occur in mainstream cigarette smoke. The other 35 have never been reported to occur in cigarette smoke. The nine agents reported are benzene, cadmium, arsenic, nickel, chromium, 2-naphthyl-amine, vinyl chloride, 4-aminobiphenyl and beryllium. The reported yields of each of these nine agents in mainstream smoke varies widely. The range of yields reported for a given compound is influenced by the type of cigarette tested and when the analysis was conducted. In micrograms/cigarette, the ranges that have been reported for each of the nine compounds are: benzene (0.05-104), cadmium (0-6.67), arsenic (0-1.4), nickel (0-0.51), chromium (0.0002-0.5), 2-naphthylamine (0.0002-0.022), vinyl chloride (0.0013-0.0158), 4-aminobiphenyl (0.00019-0.005) and beryllium (0-0.0005). Although some of the variation in reported yields may be due to differences in analytical methodology, several correlations between the yield of a particular chemical in mainstream smoke and certain cigarette characteristics were observed. For example, charcoal filtration was associated with reduced vinyl chloride, and the concentration of sodium nitrate in the tobacco was positively correlated with the mainstream yield of both 2-naphthylamine and 4-aminobiphenyl. Benzene yield in mainstream cigarette smoke was correlated with the amount of tobacco burned and with the 'tar' level. Agronomic factors such as production practices and soil characteristics, and environmental conditions such as rainfall, reportedly influence the accumulation of metals, for example, cadmium, beryllium, chromium, nickel and arsenic, in the leaf. The use of fertilizers low in nitrate and heavy metals would be expected to substantially reduce the yields of most of the "IARC Group 1 carcinogens" reported to occur in mainstream cigarette smoke. Additionally, modifications in cigarette design, for instance, the use of enhanced charcoal filters or heated instead of burned tobacco, would also be expected to reduce the yields of several of these agents.

2-Naphthylamine↗

Effect of ion modification of commonly used orthopedic materials on the attachment of human bone-derived cells.

Biomaterials which combine optimum properties of strength and biocompatibility are desirable in improving the long-term performance of implantable medical devices. Our study is aimed at developing technology designed to alter the outer atomic layers of a material to give the desired compatibility with the tissue while retaining the properties of the bulk substratum. Materials used in this study were titanium vanadium alloy (Ti-6Al-4V) and cobalt chromium molybdenum alloy (Co-Cr). Soda lime glass discs and polyethylene terephthalate (PET) acted as controls. A cathode of either Ti-6Al-4V or Co-Cr was used to simultaneously deposit and implant identified substrata. The attachment of human bone-derived cells (HBDC) to various materials was determined using radiolabeling or colorimetric assays. Results show that HBDC adhere preferentially to the unmodified surfaces of Ti-6Al-4V and Ti-6Al-4V on glass compared to the unmodified Co-Cr surfaces and to that of the Co-Cr on glass. Depositing Ti-6Al-4V on Co-Cr gives significantly better attachment of HBDC than when depositing Co-Cr onto Ti-6Al-4V. While cellular attachment to the created surfaces reflects that of the cathodic materials, it is not identical to these materials. Ion deposition/implantation is capable of creating permanent surfaces which reflect the adhesion of source materials not bulk substrata.

Alloys↗

Detoxification of tannery waste liquors with an electrolysis system.

This paper describes an electrochemical treatment and detoxification of tannery waste liquors (TWL). In this technique, TWL was passed through an electrolytic cell using a Ti/Pt anode and a stainless steel 304 cathode. Owing to the strong oxidizing potential of the chemicals produced (chlorine, oxygen, hydroxyl radicals and other oxidants) the organic and inorganic pollutants (ammonia, sulfides and chromium) were wet oxidized to carbon dioxide, nitrogen oxides and sulfur dioxide. In addition, chromium was precipitated as Cr(2)(SO(4))(3). Experiments were run in a batch, laboratory-scale, pilot-plant, and the results are reported herein. After 30 min and 3 h of electrolysis at 0.26 A cm(-2), 45 degrees C and pH 9, total chemical oxygen demand (COD) was reduced by 52 and 83% and biochemical oxygen demand (BOD(5)) was reduced by 35 and 66%, respectively. Additionally, total suspended solids (TSS) were reduced by 8.6 and 26%, total phenolic compounds were reduced by 95.6 and 99.4%. Ammonia, sulfides and soluble chromium were reduced by 100% in both cases, while the mean anode efficiency was 81 g h(-1) A(-1) m(-2) and 1.9 g h(-1) A(-1) m(-2). Also, the mean energy consumption was 4.8 kwh kg(-1) of COD reduced and 200 kwh kg(-1) of COD reduced for 0.5 and 3 h, respectively. These results strongly indicate that this electrolytic method of total oxidation of TWL cannot be cost effective for wide use. However, it can be used as an effective pretreatment stage for detoxification of the wastewater, owing to great efficiency especially with respect to COD and toxicity (phenolics) reduction.

Journal Article↗