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PubMed2000

Chromium(III)-induced 8-hydroxydeoxyguanosine in DNA and its reduction by antioxidants: comparative effects of melatonin, ascorbate, and vitamin E.

Chromium compounds are well documented carcinogens. Cr(III) is more reactive than Cr(VI) toward DNA under in vitro conditions. In the present study, we investigated the ability of Cr(III) to induce oxidative DNA damage by examining the formation of 8-hydroxydeoxyguanosine (8-OH-dG) in calf thymus DNA incubated with CrCl(3) plus H(2)O(2). We measured 8-OH-dG using HPLC with electrochemical detection. In the presence of H(2)O(2), we observed that Cr(III)-induced formation of 8-OH-dG in isolated DNA was dose and time dependent. Melatonin, ascorbate, and vitamin E (Trolox), all of which are free radical scavengers, markedly inhibited the formation of 8-OH-dG in a concentration-dependent manner. The concentration that reduced DNA damage by 50% was 0.51, 30.4, and 36.2 microM for melatonin, ascorbate, and Trolox, respectively. The results show that melatonin is 60- and 70-fold more effective than ascorbate or vitamin E, respectively, in reducing oxidative DNA damage in this in vitro model. These findings also are consistent with the conclusion that the carcinogenic mechanism of Cr(III) is possibly due to Cr(III)-mediated Fenton-type reactions and that melatonin's highly protective effects against Cr(III) relate, at least in part, to its direct hydroxyl radical scavenging ability.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Reductive activation with cysteine represents a chromium(III)-dependent pathway in the induction of genotoxicity by carcinogenic chromium(VI).

Induction of DNA damage by carcinogenic hexavalent chromium compounds [Cr(VI)] results from its reduction to lower oxidation states. Reductive metabolism of Cr(VI) generates intermediate Cr(V/IV)species, organic radicals, and finally Cr(III), which forms stable complexes with many biological ligands, including DNA. To determine the biological significance of different reaction products, we examined genotoxic responses and the formation of DNA damage during reduction of Cr(VI) by its biological reducer, cysteine. We have found that cysteine-dependent activation of Cr(VI) led to the formation of Cr-DNA and cysteine-Cr-DNA adducts as well as interstrand DNA cross-links. The yield of binary and ternary DNA adducts was relatively constant at different concentrations of Cr(VI) and averaged approximately 54 and 45%, respectively. Interstrand DNA cross-links accounted on average for 1% of adducts, and their yield was even less significant at low Cr(VI) concentrations. Reduction of Cr(VI) in several commonly used buffers did not induce detectable damage to the sugar-phosphate backbone of DNA. Replication of Cr(VI)-modified plasmids in intact human fibroblasts has shown that cysteine-dependent metabolism of Cr(VI) resulted in the formation of mutagenic and replication-blocking DNA lesions. Selective elimination of Cr-DNA adducts from Cr(VI)-treated plasmids abolished all genotoxic responses, indicating that nonoxidative, Cr(III)-dependent reactions were responsible for the induction of both mutagenicity and replication blockage by Cr(VI). The demonstration of the mutagenic potential of Cr-DNA adducts suggests that these lesions can be explored in the development of specific and mechanistically important biomarkers of exposure to toxic forms of Cr.

Biomarkers↗
PubMed2004

Signal transduction of p53-independent apoptotic pathway induced by hexavalent chromium in U937 cells.

It has been reported that the hexavalent chromium compound (Cr(VI)) can induce both p53-dependent and p53-independent apoptosis. While a considerable amount of information is available on the p53-dependent pathway, only little is known about the p53-independent pathway. To elucidate the p53-independent mechanism, the roles of the Ca(2+)-calpain- and mitochondria-caspase-dependent pathways in apoptosis induced by Cr(VI) were investigated. When human lymphoma U937 cells, p53 mutated cells, were treated with 20 microM Cr(VI) for 24 h, nuclear morphological changes and DNA fragmentation were observed. Production of hydroxyl radicals revealed by electron paramagnetic resonance (EPR)-spin trapping, and increase of intracellular calcium ion concentration monitored by digital imaging were also observed in Cr(VI)-treated cells. An intracellular Ca(2+) chelator, BAPTA-AM, and calpain inhibitors suppressed the Cr(VI)-induced DNA fragmentation. The number of cells showing low mitochondrial membrane potential (MMP), high level of superoxide anion radicals (O(2)(-)), and high activity of caspase-3, which are indicators of mitochondria-caspase-dependent pathway, increased significantly in Cr(VI)-treated cells. An antioxidant, N-acetyl-l-cysteine (NAC), decreased DNA fragmentation and inhibited the changes in MMP, O(2)(-) formation, and activation of caspase-3 induced by Cr(VI). No increase of the expressions of Fas and phosphorylated JNK was observed after Cr(VI) treatment. Cell cycle analysis revealed that the fraction of G2/M phase tended to increase after 24 h of treatment, suggesting that Cr(VI)-induced apoptosis is related to the G2 block. These results indicate that Ca(2+)-calpain- and mitochondria-caspase-dependent pathways play significant roles in the Cr(VI)-induced apoptosis via the G2 block, which are independent of JNK and Fas activation. The inhibition of apoptosis and all its signal transductions by NAC suggests that intracellular reactive oxygen species (ROS) are important for both pathways in Cr(VI)-induced apoptosis of U937 cell.

Apoptosis↗
PubMed1992

Occupational exposure to carcinogens in Finland.

Finland has kept a registry on the manufacture and use of carcinogenic agents involving occupational exposure since 1979. Employers must report annually to the labor safety authorities the employees who have been exposed to carcinogens and provide information on carcinogenic agents produced, used, or formed. Out of 131 substances or groups of agents listed as carcinogenic, occupational exposure to 78 of them was reported in 1987. About half of the agents reported were used or produced in industry and half were handled on a laboratory scale. About 15,000 employees from 1,700 work departments were reported to the registry; 17% of them were women. The number of workers reported in 1987 accounted for 0.6% of the total work force. It has been estimated that at least 60,000 workers are exposed annually to carcinogens in Finland. The three most prevalent exposures--hexavalent chromium compounds, nickel and its inorganic compounds, and asbestos--accounted for over 60% of all exposed workers; only five carcinogenic chemicals were produced in Finland in 1987.

Asbestos↗
PubMed1984

Proportion of lung cancers due to occupational exposure.

The proportions of male lung cancers due to occupational exposure and, respectively, to cigarette smoking in a highly industrialized area of Northern Italy were estimated in a population-based case-control study in 1976-9. Two hundred and four out of the 211 lung cancer cases and 351 controls sampled from the source population were questioned about their occupational and smoking histories. On the basis of the occupational history each subject was classified as probably exposed (+), possibly exposed (?), or unexposed (-) to one or more of the chemicals known to be carcinogenic for the human lung, namely asbestos, polycyclic aromatic hydrocarbons, arsenic, nickel and chromium compounds, BCME, CMME and vinyl chloride. Upon stratification by cigarette smoking, contrasting the occupationally exposed subjects, whether certainly or uncertainly defined, with the unexposed ones, the RR for lung cancer was 2.1 and the occupational etiologic fraction was 0.33 (95% confidence interval 0.19-0.47). The tobacco etiologic fraction was 0.81, while the two exposures together accounted for 89% of the total burden of incident cases. If 33% of all male lung cancers were of occupational aetiology, then this alone would represent 5% of all cancer deaths.

Aged↗
PubMed1995

Current aspects in metal genotoxicity.

While carcinogenic metal ions are mostly non-mutagenic in bacteria, different types of cellular damage have been observed in mammalian cells, which may account for their carcinogenic potential. Two modes of action seem to be predominant: the induction of oxidative DNA damage, best established for chromium compounds, and the interaction with DNA repair processes, leading to an enhancement of genotoxicity in combination with a variety of DNA damaging agents. In the case of Cd(II), Ni(II), Co(II), Pb(II) and As(III), DNA repair processes are disturbed at low, non-cytotoxic concentrations of the respective metal compounds. Even though different steps in DNA repair are affected by the diverse metals, one common mechanism might be the competition with essential metal ions.

Animals↗
PubMed1994

Direct and quantitative vitamin B12 absorption measurement in patients with disorders in the distal part of the bowel. Comparison of stool spot test [SST] with whole body counting in patients with ileal pelvic reservoir, ileostomy or Crohn's disease.

Direct and quantitative vitamin B12 absorption studies were performed in 25 patients with disorders in the distal small intestine using whole body counting as the gold standard. Simultaneously, vitamin B12 absorption was also determined by the more simple stool spot test (SST) which incorporates 51CrCl3 as a nonabsorbable marker. The SST provided a reliable direct and quantitative measure of vitamin B12 absorption in patients with previous ileal resections due to Crohn's disease (CD) (n = 7) as compared with whole body counting. In ulcerative colitis (UC) patients with either an ileal pelvic reservoir (n = 10) or a conventional ileostomy (n = 8), markedly shorter bowel transit times and absence of colon may have hindered sufficient mixture of the tracer and marker isotopes which could explain the false absorption values according to the SST in single patients. Therefore, an intact colon and a near-normal bowel transit time seem to be essential for performance of the SST. Whole body counting showed, as expected, that all CD patients except one had decreased vitamin B12 absorption (median 23%; range 3-39%) (normally > 35%). In UC patients with ileostomy, only one had a markedly decreased vitamin B12 absorption, two borderline normal values, while the rest had normal values (median 54%, range 15-76%). All UC patients with ileal pelvic reservoir had normal vitamin B12 absorption values (median 40.5%, range 36-87%). We conclude that vitamin B12 substitution therapy is probably required in patients with CD with ileal resection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1982

Corrosion of orthodontic bracket bases.

Attention has recently been focused on the development of black and green stains in association with directly bonded stainless steel brackets. Twelve clinical cases of staining were studied in this investigation. After intraoral photography of the stains, the brackets were removed for examination with the scanning electron microscope. Multiple voids were observed at the resin-bracket interface, especially at the periphery. Considerable deterioration of the alloy base and mesh structure was observed in the void areas. Preliminary analysis of the stains showed that chromium compounds were present. The findings suggested that the presence of voids, together with poor oral hygiene, led to crevice corrosion of the Type 304 stainless steel and formation of colored corrosion products which can result in enamel stains. The use of stainless steels of improved corrosion resistance is recommended to overcome this problem.

Chemical Phenomena↗
PubMed1986

Use of a gamma-labeled bile acid (75SeHCAT) as a test of ileal function. Methods of improving accuracy.

The object of the present study was to improve the accuracy of measurements of ileal function obtained by abdominal scanning and fecal counting after oral administration of the gamma-labeled bile acid 75seleno-homocholic acid-taurine (75SeHCAT), as current techniques do not distinguish between retention of the bile acid within the enterohepatic circulation from retention within the colon, and are also affected by incomplete stool collection when using the fecal method. We have therefore introduced the following modifications: (a) simultaneous ingestion of 51CrCl3 as a nonabsorbable correction marker for both the abdominal scanning and fecal counting methods; and (b) the use of 75SeHCAT counts over the gallbladder area on abdominal scanning, because these counts should be independent of colonic retention. We have studied 42 subjects, including 6 healthy controls, 6 ileal resection subjects, 15 ulcerative colitis patients, and 15 patients with unresected ileal Crohn's disease. Colonic retention (0%-68% per day) caused a variable overestimate of 75SeHCAT absorption. Corrected measurements of the fecal absorption index determined by a gamma-counter and of the abdominal absorption coefficient determined by a gamma-camera correlated well with each other (r = 0.92, p less than 0.0001), providing an internal validation of the 51CrCl3 modification. The fecal absorption index could also be determined from the carmine-rich stool collection of a single day, and this also correlated well with the abdominal absorption coefficient (r = 0.81, p less than 0.0001). Gallbladder scanning alone was simpler, involving only one isotope, but it correlated less well with the fecal absorption index than did the abdominal absorption coefficient (r = -0.64, p less than 0.001).

Adult↗
PubMed1984

Metal-induced mutagenesis in the lacI gene of Escherichia coli.

Mutagenesis in the lacI gene of Escherichia coli has been examined in cells grown in the presence of beryllium, manganese or chromium compounds, metals with suspected mutagenic or carcinogenic potential. 2--3-fold increases in mutation frequency were produced by BeCl2, MnCl2 and K2Cr2O7. Among the cells grown in the presence of Be2+, the frequency of amber and ochre mutants was 3-fold higher than the spontaneous background, suggesting that at least part of the increased mutagenicity was due to base-substitution mutations. The specificity of base-substitution mutations induced by Be2+ and Mn2+ in the lacI gene was analyzed. Among the amber mutations induced in cells grown in the presence of Be2+, an increase in G:C----A:T transitions was detected. In contrast, following growth in Mn2+, no increase in amber and ochre mutation frequencies was observed, and the mutational spectrum resembled that obtained spontaneously indicating that mutations induced by Mn2+ in the lacI gene involve changes that do not yield nonsense mutations. These results suggest that metals may exert a number of different mutagenic effects and that these effects vary for each metal.

Beryllium↗
PubMed1989

Comparison of polyethylene glycol and chromium-51 chloride as nonabsorbable stool markers in calcium balance studies.

The day-to-day variations in stool calcium content during calcium balance studies are usually corrected for by adjusting for the recovery of an orally administered nonabsorbable stool marker. We describe here a simple method for making this correction using chromium-51 chloride hexahydrate (51Cr) in balance studies. This approach was developed because of difficulties encountered with the more widely used marker, polyethylene glycol (PEG). With one batch of PEG, the stool recovery was only 81% (whereas with 51Cr it was 95%). The reason for this poor recovery was contamination of the PEG 4000 with a high molecular weight species (10-15%, wt/wt). Because others have also reported low PEG recoveries and because we found that the chemical abnormality in the PEG was very difficult to detect, we believe that 51Cr is more reliable and should be the preferred stool marker for the calcium balance studies.

Administration, Oral↗
PubMed1993

Hexavalent chromium produces DNA strand breakage but not unscheduled DNA synthesis at sub-cytotoxic concentrations in hepatocytes.

Rat hepatocytes were used to investigate the possible induction of unscheduled DNA synthesis (UDS) and the extent of DNA strand breaks induced by sodium dichromate (a representative chromium(VI) compound) and chromium acetate hydroxide (chromium(III)) in vitro. Cytotoxicity, measured using tetrazolium salt (MTT) reduction assay, was found at a much higher dose of chromium(III), (> 50 microM), compared to that of chromium(VI), (> 2.5 microM), in cultured hepatocytes over 20 h treatment at 37 degrees C. Chromium(VI), but not chromium(III), stimulated minimal UDS in hepatocytes at sub-cytotoxic concentrations. A positive UDS response was only observed at cytotoxic concentration. DNA strand breaks in hepatocytes were induced by chromium(VI) following incubation at 37 degrees C for 1 h at doses of 10, 20 and 40 microM sodium dichromate. The subsequent ligation of such strand breaks in hepatocytes treated with 40 microM chromium(VI) for 1 h at 37 degrees C was demonstrated. The majority of strand breaks was repaired within 30 min following removal of the chromate. In conclusion, chromate-induced DNA strand breakage, possibly involving the formation of oxygen radicals and lack of significant UDS have some analogy to those produced by ionizing radiation.

Animals↗
PubMed2004

Removal of direct red 12B and methylene blue from water by adsorption onto Fe (III)/Cr (III) hydroxide, an industrial solid waste.

Removal of direct red 12B and methylene blue by adsorption onto Fe (III)/Cr (III) hydroxide was studied using various parameters such as agitation time, dye concentration, adsorbent dose and pH. Equilibrium adsorption data followed both Langmuir and Freundlich isotherms. Adsorption followed second-order rate kinetics. The Langmuir adsorption capacity (Qo) was found to be 5.0 and 22.8 mg dye per g of the adsorbent for direct red 12B and methylene blue, respectively. Acidic pH was favorable for the adsorption of direct red 12B and basic pH for methylene blue. Desorption studies showed that chemisorption seems to be the major mode of adsorption.

Adsorption↗
PubMed2005

Combustion of chlorinated volatile organic compounds (VOCs) using bimetallic chromium-copper supported on modified H-ZSM-5 catalyst.

The paper reports on the performance of chromium or/and copper supported on H-ZSM-5(Si/Al = 240) modified with silicon tetrachloride (Cr1.5/SiCl4-Z, Cu1.5/SiCl4-Z and Cr1.0Cu0.5/SiCl4-Z) as catalysts in the combustion of chlorinated VOCs (Cl-VOCs). A reactor operated at a gas hourly space velocity (GHSV) of 32,000 h(-1), a temperature between 100 and 500 degrees C with 2500 ppm of dichloromethane (DCM), trichloromethane (TCM) and trichloroethylene (TCE) is used for activity studies. The deactivation study is conducted at a GHSV of 3800 h(-1), at 400 degrees C for up to 12 h with a feed concentration of 35,000 ppm. Treatment with silicon tetrachloride improves the chemical resistance of H-ZSM-5 against hydrogen chloride. TCM is more reactive compared to DCM but it produces more by-products due to its high chlorine content. The stabilization of TCE is attributed to resonance effects. Water vapor increases the carbon dioxide yield through its role as hydrolysis agent forming reactive carbocations and acting as hydrogen-supplying agent to suppress chlorine-transfer reactions. The deactivation of Cr1.0Cu0.5/SiCl4-Z is mainly due to the chlorination of its metal species, especially with higher Cl/H feed. Coking is limited, particularly with DCM and TCM. In accordance with the Mars-van Krevelen model, the weakening of overall metal reducibility due to chlorination leads to a loss of catalytic activity.

Air Pollutants, Occupational↗
PubMed2006

Testicular dysfunction and antioxidative defense system of Swiss mice after chromic acid exposure.

Chromic acid (CrO(3)), a hexavalent compound of chromium (Cr) that is widely used in different industries, has been associated with reproductive abnormalities in male Swiss mice. The mechanism of male reproductive toxicity is not clear. Metal-induced reactive oxygen species (ROS) may impair spermatogenesis or alter sperm morphology. Therefore, in the present study we investigated the induction of oxidative stress in the testes of mice over time (5th-8th weeks) after a single intraperitoneal dose (1mg/kg body weight) of CrO(3). Exposed animals showed significantly decreased sperm counts and markedly increased rates of sperm abnormality. Oxidative stress was measured in terms of malondialdehyde content, the activities of superoxide dismutase, peroxidase, and catalase, and non-enzymatic antioxidants such as ascorbic acid. The significant changes in exposed groups relative to controls suggest that CrO(3) exposure suppressed antioxidant enzymes and ascorbic acid with a concomitant increase in the level of lipid peroxidation and H(2)O(2) to adversely affect testicular function.

Animals↗
PubMed1997

Effects of dietary consumption of black tea infusion alone and in combination with known clastogens on mouse bone marrow chromosomes in vivo.

Black tea infusion in water, in concentrations simulating human consumption, was administered by gavage daily to male Swiss mice for 7 days. One set was given tea once daily and the other twice daily. The mice were then exposed to two known clastogens: chromium (VI) as potassium dichromate and mitomycin C on day 7, and killed after 24 hr. Chromosome damage was studied in preparations made from bone marrow following colchine injection of all mice, and examination of the cells after pretreatment in hypotonic solution, fixation, air drying one and staining with Giemsa solution. No effect was observed in mice given tea once daily. In mice administered tea twice daily, the frequencies of chromosomal aberrations and damaged cells were increased as compared with those of the control in distilled water. Administration of tea twice daily for 7 days could not reduce the clastogenic effects of mitomycin C significantly. The damage due to potassium dichromate was reduced significantly, almost to the level of distilled water. Dietary administration of black tea infusion could therefore significantly protect against clastogenic activity of chromium compounds though it was itself mildly clastogenic.

Analysis of Variance↗