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[Bronchopulmonary precancerous conditions and tumors--risk groups from the occupational medicine viewpoint].

Risk groups with regard to bronchopulmonary precancerous and tumor diseases of occupational origin can be deduced from current occupational disease statistics. Most prominent are those working with asbestos. Each year about 250 asbestos-associated bronchial carcinomas and 400 mesotheliomas are recognized and compensated; the tendency is increasing. Because of the long latency time, the frequency peak will probably be reached in about 15 years in spite of the prohibition of asbestos usage. The second place is probably taken by malignomas among the underground uranium mine workers in Thuringia and Saxony (SDAG Wismut). Next come bronchial carcinomas with silicosis (carcinoma in scar tissue) after exposure to chromium(VI) and arsenic compounds as well as various other chemicals and metals. Dose-activity relationships are significant for all occupational carcinogenic agents, as there are also often syncancerogenic influences (especially smoking). From the data on previous loading, high risk groups, for example, among the insulation workers exposed to asbestos or uranium miners in the so-called "wild years", can be defined. A suitable screening method for the detection of bronchopulmonary tumors in the early stages has not yet been established. Medical checkups for the respective risk groups concentrate on the early X-ray detection of circular foci. As shown by recent studies, cytological sputum diagnosis, (fluorescence) bronchoscopy, and BAL cytology must be employed much more frequently in the high risk groups so that the prognostically more favorable stages of preneoplasm and carcinoma in situ can be detected and possibly treated curatively. These procedures are currently reaching a considerably higher sensitivity with the help of modern molecular biology techniques (e.g. detection of tumor-associated genetic changes and gene products). This contributes to an improvement in surveillance examinations with increasing detection of the curable early forms of tumors. However, only the further development of primary prevention, i.e. the greatest possible minimization or, if possible, total elimination of contact with carcinogenic agents and the consequent control of occupational protection will lead to a drastic reduction in the occupational risk of cancer.

Carcinoma, Bronchogenic↗

Speciation analysis of arsenic and selenium compounds by capillary electrophoresis.

High-performance capillary electrophoresis is applied to the separation of different inorganic and organic arsenic and selenium compounds. In comparison with UV-detection, an approach with conductivity detection is described expecting higher sensitivity and universality. In this case the capillary was statically modified with CTAB before the electromigration procedure. The separation was performed with an electrolyte system consisting of CHES and Triton X-100. Detection limits of 0.06 mg/L or lower were obtained for As(V) and Se(VI). Water samples of an arsenic-polluted tailing of tin mining processes were analysed for anions as well as arsenic and selenium species.

Journal Article↗

Chemotherapy of CNS-trypanosomiasis: the combined use of the arsenicals and nitro-compounds.

In trypanosomiasis chemotherapy the main mode of action of the nitro-compounds, including the 5-nitroimidazoles or nitrofurans (nifurtimox) is to increase the oxidative stress on the organism either directly by the production of peroxides or indirectly by "futile redox cycling". If this is the case, then these nitro-compounds and the arsenicals should act in combination on the trypanothione oxidation-reduction reaction of the trypanosome. In this paper this has been demonstrated to occur with all those nitro-compounds which have exhibited reasonable trypanocidal action in monotherapy or other combination chemotherapeutic regimens. A major advantage is the short treatment period of approximately 5 days. Pretreatment with a single dose of suramin increased the efficacy of the nitroimidazole-arsenical combination.

Animals↗

Arsenic trioxide and melarsoprol induce apoptosis in plasma cell lines and in plasma cells from myeloma patients.

Recent data have renewed the interest for arsenic-containing compounds as anticancer agents. In particular, arsenic trioxide (As2O3) has been demonstrated to be an effective drug in the treatment of acute promyelocytic leukemia by inducing programmed cell death in leukemic cells both in vitro and in vivo. This prompted us to study the in vitro effects of As2O3 and of another arsenical derivative, the organic compound melarsoprol, on human myeloma cells and on the plasma cell differentiation of normal B cells. At pharmacological concentrations (10(-8) to 10(-6) mol/L), As2O3 and melarsoprol caused a dose- and time-dependent inhibition of survival and growth in myeloma cell lines that was, in some, similar to that of acute promyelocytic leukemia cells. Both arsenical compounds induced plasma cell apoptosis, as assessed by 4',6-diamidino-2-phenylindole staining, detection of phosphatidylserine at the cell surface using annexin V, and by the terminal deoxynucleotidyl transferase-mediated nick end labeling assay. As2O3 and melarsoprol also inhibited viability and growth and induced apoptosis in plasma-cell enriched preparations from the bone marrow or blood of myeloma patients. In nonseparated bone marrow samples, both arsenical compounds triggered death in myeloma cells while sparing most myeloid cells, as demonstrated by double staining with annexin V and CD38 or CD15 antibodies. In primary myeloma cells as in cell lines, interleukin 6 did not prevent arsenic-induced cell death or growth inhibition, and no synergistic effect was observed with IFN-alpha. In contrast to As2O3, melarsoprol only slightly reduced the plasma cell differentiation of normal B cells induced by pokeweed mitogen. Both pokeweed mitogen-induced normal plasma cells and malignant plasma cells showed a normal nuclear distribution of PML protein, which was disrupted by As2O3 but not by melarsoprol, suggesting that the two arsenical derivatives acted by different mechanisms. These results point to the use of arsenical derivatives as investigational drugs in the treatment of multiple myeloma.

Antineoplastic Agents↗

Testicular toxicity evaluation of arsenic-containing binary compound semiconductors, gallium arsenide and indium arsenide, in hamsters.

The testicular toxicities of gallium arsenide (GaAs), indium arsenide (InAs) and arsenic trioxide (As2O3) were examined by repetitive intratracheal instillation using hamsters. GaAs (7.7 mg/kg) and As2O3 (1.3 mg/kg) were instilled twice a week a total of 16 times and InAs (7.7 mg/kg) was instilled a total of 14 times. GaAs caused testicular spermatid retention and epididymal sperm reduction, though the degrees were less severe than those in rats shown in our previous experiment. InAs and As2O3 did not show any testicular toxicities. Serum arsenic concentration in GaAs-treated hamsters was less than half of that in As2O3-treated hamsters in which no testicular toxicities were found. Serum molar concentration of gallium was 32-times higher than that of arsenic in GaAs-treated hamsters. Therefore gallium may play a main role in the testicular toxicity of GaAs in hamsters.

Animals↗

Speciation of arsenic and selenium compounds by ion-pair reversed-phase chromatography with electrothermic atomic absorption spectrometry. Application of experimental design for chromatographic optimisation.

An off-line system is proposed consisting of ion-pair reversed-phase liquid chromatography, collections of fractions at the outflow of the column and furnace atomic absorption spectrometry. The so-called system allowed determination of both arsenic and selenium species mainly found in the environment and in mammals (arsenite, arsenate, monomethylarsonate, dimethylarsinate, selenite, selenate, selenocystamine, selenocystine, selenomethionine and selenoethionine). In order to study the retention behaviour of these compounds and to estimate the optimal conditions for the chromatographic separation, central composite designs were used to evaluate the influence of the eluent parameters such as pH, tetrabutylammonium phosphate (TBA) concentration and sodium hydrogenphosphate amounts. The retention factors of each species and the selectivity were established as response criteria. Response surfaces and isoresponse curves were drawn from the mathematical models and enabled one to determine the optimal conditions and to visualise the method robustness. The predicted optimal zone was situated at pH 5.5-6.5, 4.0 mM Na2HPO4 and 3.0-4.0 mM TBA. Regression models suggested linearity for the studied compounds in the range 25-200 microg selenium and arsenic per litre investigated.

Arsenic↗

Present possibilities for the determination of inorganic arsenic and organoarsenical compounds in biological fluids.

A survey is presented of the applicability of atomic spectrometry and other techniques for the quantitation of both inorganic and organic arsenic in biological fluids. Pretreatment of samples and speciation of the different As forms are particularly emphasized. The potential of inductively-coupled plasma spectrometry combined with high performance liquid chromatography separations is also highlighted.

Arsenic↗

[Arsenic poisoning].

BACKGROUND: Arsenic poisoning has been discussed frequently in Norway during the past year on the background of a suspected crime case. There seem to be several uncertainties regarding this issue, also in the medical profession. MATERIAL AND METHODS: We have searched the literature and made a review based upon the present knowledge about arsenic and arsenic poisoning. RESULTS: Arsenic can be found in numerous chemical compounds with different properties. Inorganic arsenic compounds, like arsenic trioxide, are reactive and can cause damage to the body. Organic arsenic compounds, which are found in high concentrations in fish and shellfish, are not considered toxic. Ingestion of inorganic arsenic affects cellular energy production; lethal poisonings can occur. Common clinical features after acute intoxication with arsenic are dysphagia, nausea, vomiting, abdominal pain, diarrhoea, intense thirst, and muscle cramps. Clinical features of chronic poisoning are hyperkeratosis in the palms and foot soles, pigmentation and conjunctivitis. INTERPRETATION: Arsenic poisoning is a rare condition; its clinical features are uncharacteristic and the diagnosis must be confirmed by analysis of blood, urine and hair.

Arsenates↗

The background state leading to arsenic contamination of Bengal basin groundwater.

The Bengal basin has the world's densest water diversion constructions on the natural courses of rivers. The most damaging water diversion construction is the Farakka Barrage upon the international River Ganges. The diversion of water through this barrage and other constructions upstream of it has reduced the Ganges flow rate by 2.5 times. The resulting downstream effects are the depletion of surface water resources, more withdrawal than recharge of groundwater, sinking groundwater table, spread in depth and extension of the vadose zone, changes in surface features, climatic changes, etc. An investigation was carried out to find the contributions of water diversion to the arsenic contamination of groundwater in the Bengal basin. The reasonable scenario for arsenic contamination is the oxygen deficiency in groundwater and aeration of arsenopyrites buried in the sediment that would remain under water prior to 1975. The mineral forms water-soluble compounds of arsenic when react with atmospheric oxygen. These soluble arsenic compounds infiltrates to the groundwater. This article summarizes the short-time and incomplete study-based quick conclusions reached by investigators that have totally avoided the vital issue of water diversion. It then shows the depleting condition of the water resources under continuing diversions, the generation of favorable condition for arsenic release, the reasons for low sulfur concentration, the reason for first contamination in the Hugly basin, and the hindrance to water's self-purification. The articles advocates that the restoration of the virgin wetland ecosystems in the Bengal basin following the stoppage of the inordinate amount of unilateral upstream water withdrawals can remove the catastrophe.

Arsenic↗

Pink-eyed dilution protein modulates arsenic sensitivity and intracellular glutathione metabolism.

Mutations in the mouse p (pink-eyed dilution) and human P genes lead to melanosomal defects and ocular developmental abnormalities. Despite the critical role played by the p gene product in controlling tyrosinase processing and melanosome biogenesis, its precise biological function is still not defined. We have expressed p heterologously in the yeast Saccharomyces cerevisiae to study its function in greater detail. Immunofluorescence studies revealed that p reaches the yeast vacuolar membrane via the prevacuolar compartment. Yeast cells expressing p exhibited increased sensitivity to a number of toxic compounds, including arsenicals. Similarly, cultured murine melanocytes expressing a functional p gene were also found to be more sensitive to arsenical compounds compared with p-null cell lines. Intracellular glutathione, known to play a role in detoxification of arsenicals, was diminished by 50% in p-expressing yeast. By using the glutathione-conjugating dye monochlorobimane, in combination with acivicin, an inhibitor of vacuolar gamma-glutamyl cysteine transpeptidase, involved in the breakdown of glutathione, we found that p facilitates the vacuolar accumulation of glutathione. Our data demonstrate that the pink-eyed dilution protein increases cellular sensitivity to arsenicals and other metalloids and can modulate intracellular glutathione metabolism.

Acid Phosphatase↗

Combined use of photocatalyst and adsorbent for the removal of inorganic arsenic(III) and organoarsenic compounds from aqueous media.

A novel method for the removal of inorganic arsenic(III) (As(III)), monomethylarsonate (MMA), and dimethylarsinate (DMA) from aqueous media, was proposed and investigated. This method involves the combined use of TiO2-photocatalyst and an adsorbent, which has a high ability of As(V) adsorption, under photo-irradiation. When an aqueous solution of As(III) was stirred and irradiated by sunlight or xenon lamp in the presence of TiO2 suspension, the oxidation of As(III) into As(V) was effectively attained. By use of the same photocatalytic reaction, MMA and DMA were also degraded into As(V), while the total organic carbon (TOC) in the aqueous phase was decreased. When an aqueous solution of As(III) was stirred with a mixed suspension of TiO2 and an adsorbent for As(V) (activated alumina) under sunlight irradiation, the arsenic removal reached 89% after 24 h. By use of the same photocatalyst-adsorbent system, 98% of MMA and 97% of DMA were removed. The mechanism of the removal of arsenic species by the photocatalyst-adsorbent system was discussed.

Adsorption↗

Metals as mutagens.

A number of metals are mutagenic in bacteria or phage. These include compounds of arsenic, chromium, copper, iron, manganese, molybdenum, platinum, and selenium. Compounds containing alumium, antimony, arsenic, cadmium, copper, lead, mercury, nickel, and tellium have been shown to induce chromosomal aberrations or abnormal cell divisions in animal or plant cells. Genetic evidence suggests that arsenic, chromium, and molybdenum compounds may influence the accuracy of DNA repair processes in microorganisms.

Animals↗