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Airborne cadmium and carcinogenesis of the respiratory tract.

Exposure to airborne cadmium occurs mainly at the workplace. Significant exposure also occurs through smoking. Results of a recent epidemiologic study suggest that occupational inhalation of cadmium is connected with an increased lung cancer risk. This finding corroborates the high lung cancer incidence found among rats after chronic low-level exposure to cadmium chloride aerosols. Differences in the tumor sites, exposure conditions, and the pulmonary metabolism of cadmium between rodents and man make it difficult to extrapolate quantitatively from rats to humans. In contrast to the workplace, concentrations of cadmium in ambient air are very low, and the risk of lung cancer is probably very low, even for people living close to cadmium-emitting industries. The chemical form of inhaled cadmium appears to be important. While cadmium oxide and cadmium chloride seem to be equally toxic, cadmium sulfide exhibits a lower acute pulmonary toxicity. However, whether this is also true for carcinogenic effects is not known. Additional long-term inhalation studies with animals and further evaluation of epidemiologic studies are necessary to answer questions about the carcinogenic potency of cadmium compounds of different chemical form. As long as such results are not available, it is prudent to regard all cadmium compounds as having a carcinogenic potential.

Air Pollutants, Occupational↗

Effect of N-benzyl-D-glucamine dithiocarbamate on distribution and excretion of cadmium in rats.

The effect of sodium N-benzyl-D-glucamine dithiocarbamate (NBG-DTC) on the distribution and excretion of cadmium in rats exposed to cadmium and the chemical form and intestinal reabsorption of cadmium compound excreted in the bile were studied. Rats were injected intraperitoneally with 109CdCl2 (1 mg Cd and 10 microCi 109Cd/kg) and 24 h later, they were injected with NBG-DTC (400 or 1200 mumol/kg). The biliary excretion of cadmium was remarkably increased by intraperitoneally injection of NBG-DTC, while there was only a small increase in urinary excretion of cadmium. Such an enhancement effect of NBG-DTC on the biliary excretion of cadmium was much larger at the high dose (1200 mumol/kg) of NBG-DTC. The treatment with NBG-DTC significantly decreased the cadmium content in the liver at the dose of 1200 mumol/kg and did not result in the undesirable redistribution of cadmium to the tissues, such as brain, testes, heart and lung. In addition, it was found that the cadmium compound excreted in the bile was mainly characterized as cadmium-NBG-DTC and which was not reabsorbed from the intestinal tracts.

Animals↗

[Effect of cadmium and lead compounds on behavior of some enzymes in peripheral blood of rats with experimental diabetes].

The aim of these tests was to show whether in an experimental diabetes toxic compounds of the cadmium and lead would intensify changes in the enzymes activity caused by a diabetes itself. The test was carried out on the Wistar breed of rats. After inducing the experimental diabetes animals were given cadmium and lead compounds by searchers directly into their stomachs. The following enzymes the AspAT and the AlAT and the alkaline phosphatase (AP) were indicated among all tested animals. The statistic significant increase of the AspAT and the AlAT and the decrease of the alkaline phosphatase in a blood were documented in the experimental diabetes as well as among animals subjected to the cadmium and lead in comparison with the results secured from the checking group of animals. In comparison to animals with a diabetes itself, in the experimental diabetes the toxic compounds of the cadmium and lead explicitly increased the activity changes of the AlAT and the alkaline phosphatase. On the grounds of the above results it can be assumed that in the diabetic diseases the toxic metals may intensify pathological changes.

Alanine Transaminase↗

[Placental transfer of cadmium in pregnant women].

To clarify the maternal-fetal transfer of cadmium across the placenta, cadmium was determined in 21 paired samples of maternal blood, placenta and umbilical cord blood obtained at delivery from pregnant women who did not smoke and had no particular exposure to cadmium compounds in their history. Cadmium was detected in all the samples. In both maternal blood and umbilical cord blood, the cadmium concentrations in the red blood cells were remarkably higher than those in the plasma. The cadmium concentration in the umbilical cord blood was significantly lower than that in the maternal blood, suggesting that the placenta might effectively block the transfer of cadmium to fetuses in pregnant women. The placental cadmium concentration was the highest in the samples determined. The ratios of placental to maternal blood cadmium concentration were very large, indicating that cadmium preferentially accumulates in the placental tissues. On the other hand, the ratios of umbilical cord blood to placental cadmium concentration were very small, indicating that the placenta constitutes an effective barrier against cadmium; that is, the placental cadmium is hard to transfer to fetuses in pregnant women. The significantly positive correlations between maternal blood and placenta, between placenta and umbilical cord blood and between maternal blood and umbilical cord blood in terms of the concentrations of cadmium suggest that the amount of cadmium accumulated in placenta and transferred from mother to fetus is strongly influenced by the cadmium body burden of the mother.

Cadmium↗

Lung cancer mortality in a cohort of workers employed at a cadmium recovery plant in the United States: an analysis with detailed job histories.

OBJECTIVES: To identify and measure any relations between occupational exposure to cadmium compounds (oxide, sulphide, and sulphate) and the risk of mortality from lung cancer. METHODS: The mortality experience of 571 male production workers from a cadmium recovery facility in the United States was investigated for the period 1940-82. All study subjects were first employed in the period 1926-69; they had all been employed for at least six months between 1 January 1940 and 31 December 1969. Newly abstracted detailed job histories for the period 1926-76 were combined with assessments of exposures to cadmium over time to develop individual estimates of cumulative exposure to cadmium (total exposure and exposures received both in the presence and absence of "high" exposures to arsenic trioxide). Poisson regression was used to investigate risks of mortality from lung cancer in relation to four concentrations of cumulative exposure to cadmium (< 400, 400-999, 1000-1999, > 2000 mg.m-3.days). RESULTS: After adjustment for age attained, year of hire, and Hispanic ethnicity, there was a significant positive trend (P < 0.05) between cumulative exposure to cadmium and risks of mortality from lung cancer. Relative to a risk of unity for the lowest exposure category (first level), risks were 2.30 (95% confidence interval (95% CI) 0.72 to 7.36), 2.83 (95% CI 0.75 to 10.72), and 3.88 (95% CI 1.04 to 14.46) for the second, third, and fourth categories, respectively. Similar findings were obtained after adjustment for age only. Trends were more pronounced when employment histories were lagged first by 10 years and then by 20 years. A separate analysis examined the independent effects of exposure to cadmium received in the presence of high exposures to arsenic trioxide (mainly cadmium oxide) and exposures to cadmium received without such exposure to arsenic (mainly cadmium sulphide and cadmium sulphate). A significant trend for a risk of lung cancer was found only for exposures to cadmium received in the presence of arsenic trioxide. CONCLUSIONS: Hypotheses which are consistent with the study findings include: (a) cadmium oxide in the presence of arsenic trioxide is a human lung carcinogen, (b) cadmium oxide and arsenic trioxide are human lung carcinogens and cadmium sulphate and cadmium sulphide are not (or they are less potent carcinogens), or (c) arsenic trioxide is a human lung carcinogen and cadmium oxide, cadmium sulphate, and cadmium sulphide are not. There were only 21 deaths from lung cancer available for this analysis and it is impossible to gauge which, if any, of these hypotheses are correct.

Arsenic Trioxide↗

Lung cancer mortality in UK nickel-cadmium battery workers, 1947-2000.

AIMS: To investigate mortality from lung cancer in nickel-cadmium battery workers in relation to cumulative exposure to cadmium hydroxide. METHODS: The mortality of a cohort of 926 male workers from a factory engaged in the manufacture of nickel-cadmium batteries in the West Midlands of England was investigated for the period 1947-2000. All subjects were first employed at the plant in the period 1947-75 and employed for a minimum period of 12 months. Work histories were available for the period 1947-86; the factory closed down in 1992. Two analytical approaches were used, indirect standardisation and Poisson regression. RESULTS: Based on serial mortality rates for the general population of England and Wales, significantly increased mortality was shown for cancers of the pharynx (observed (Obs) 4, expected (Exp) 0.7, standardised mortality ratio (SMR) 559, p<0.05), non-malignant diseases of the respiratory system (Obs 61, Exp 43.0, SMR 142, p<0.05), and non-malignant diseases of the genitourinary system (Obs 10, Exp 4.1, SMR 243, p<0.05). Non-significantly increased SMRs were shown for lung cancer (Obs 45, Exp 40.7, SMR 111) and cancer of the prostate (Obs 9, Exp 7.5, SMR 116). Estimated cumulative cadmium exposures were not related to risks of lung cancer or risks of chronic obstructive pulmonary diseases, even when exposure histories were lagged first by 10, then by 20 years. CONCLUSIONS: The study findings do not support the hypotheses that cadmium compounds are human lung carcinogens.

Adolescent↗

Dermal toxicity and percutaneous absorption of cadmium in rats and mice.

Cadmium is a common contaminant in sawdust and other materials used in laboratory animal bedding. This study was conducted to assess the irritancy of a soluble cadmium compound to the skin and percutaneous absorption of the cadmium ion. Cadmium chloride solution was administered to the shaved skin of the dorsum of rats and mice daily for 10 days at concentrations of 1.0, 0.1, and 0.01% (wt/vol). Cadmium accumulated in the skin in association with approximately 6,000 ng/g in animals exposed to the high dose. Skin damage of hyperkeratosis and acanthosis with some ulcerative change was dose-related. The mitotic index in mouse skin was increased up to twofold. In rat blood, concentrations of cadmium, after 10 days of administration of a 1% concentration, were 11.65 micrograms/L, indicating percutaneous absorption. Clear evidence was seen of an accumulation of cadmium in the liver (526 ng/g) and kidney (216 ng/g), but histopathologic evidence of damage was absent, after this period at least. Concentrations of zinc were increased in the skin, probably as a consequence of local increases in metallothionein, a zinc-binding protein.

Administration, Cutaneous↗

Sildenafil citrate (Viagra) complexes with bivalent ions.

The interaction of Ca(2+)-ions with sildenafil citrate (Viagra) leads to the precipitation of a new polymorph variety of sildenafil base. Under the same conditions, Mg(2+), Zn(2+), and Cd(2+) ions form structurally related crystalline complexes of the composition Me(2+)C(28)H(34)N(6)O(11)S. Lattice parameters have been determined showing that magnesium compound belongs to an orthorhombic system, while the zinc and cadmium compounds are its monoclinic distortions. All three compounds are thermally stable, undergoing decomposition above 175 degrees C with the consequent formation of carbonates Me(2+)CO(3) and oxides.

Cations, Divalent↗

Cadmium, gene regulation, and cellular signalling in mammalian cells.

Effects of the carcinogenic metal cadmium on the regulation of mammalian gene expression are reviewed and discussed in the light of observations on interference with cellular signal transduction pathways. Cadmium ions are taken up through calcium channels of the plasma membrane of various cell types, and cadmium is accumulated intracellularly due to its binding to cytoplasmic and nuclear material. At elevated cytotoxic concentrations, cadmium inhibits the biosyntheses of DNA, RNA, and protein, and it induces lipid peroxidation, DNA strand breaks, and chromosome aberrations. Cadmium compounds as such are only weak mutagens and clastogens. However, cadmium at noncytotoxic doses interferes with DNA repair processes and enhances the genotoxicity of directly acting mutagens. Hence, the inhibition of repair and detoxifying enzymes by this metal may partially explain the observed weak genotoxic properties of this metal. Nongenotoxic mechanisms upregulating intracellular signalling pathways leading to increased mitogenesis are discussed as major mechanisms for the interpretation of the carcinogenic activity by chronic cadmium exposure. About 1 microM cadmium stimulates DNA synthesis and cell proliferation in various cell lines, whereas more elevated concentrations are inhibitory. Cadmium enhances the expression of several classes of genes at concentrations of a few microM. It stimulates the expression of immediate early genes (c-fos, c-jun, and c-myc), of the tumor suppressor gene p53, and of genes coding for the syntheses of protective molecules, including metallothioneins, glutathione, and stress (heat shock) proteins. The mechanisms underlying the modulation of gene activity by cadmium are discussed in terms of interference with cellular signalling at the levels of cell surface receptors, cellular calcium and zinc homeostases, protein phosphorylation, and modification of transcription factors. In considering the available evidence, the carcinogenic properties of cadmium are interpreted using a multifactorial approach involving indirect genotoxicity (interference with DNA repair) and the upregulation of mitogenic signalling pathways.

Animals↗

Use and possibilities for substitution of cadmium stabilizers.

Of all plastics, Polyvinyl chloride is the only product stabilized with cadmium compounds, and then only to a certain extent. The amount of cadmium used as stabilizers is approximately 15% of the world production. The general importance of stabilization in view of ecotoxicological problems is discussed, leading to a more detailed consideration of the specific sectors in which plastic materials are used. Stabilization is strongly connected with the intended application and processing technology. It is obvious that stabilization of rigid PVC is indispensable in outdoor applications. If, at present, no substitute for cadmium stabilization is available, it is emphasized that the industry is strongly interested in resolving the problem, i.e., in searching for a cadmium-free stabilizer, for economic as well as environmental reasons.

Cadmium↗

Hazards of heavy metal contamination.

The main threats to human health from heavy metals are associated with exposure to lead, cadmium, mercury and arsenic. These metals have been extensively studied and their effects on human health regularly reviewed by international bodies such as the WHO. Heavy metals have been used by humans for thousands of years. Although several adverse health effects of heavy metals have been known for a long time, exposure to heavy metals continues, and is even increasing in some parts of the world, in particular in less developed countries, though emissions have declined in most developed countries over the last 100 years. Cadmium compounds are currently mainly used in re-chargeable nickel-cadmium batteries. Cadmium emissions have increased dramatically during the 20th century, one reason being that cadmium-containing products are rarely re-cycled, but often dumped together with household waste. Cigarette smoking is a major source of cadmium exposure. In non-smokers, food is the most important source of cadmium exposure. Recent data indicate that adverse health effects of cadmium exposure may occur at lower exposure levels than previously anticipated, primarily in the form of kidney damage but possibly also bone effects and fractures. Many individuals in Europe already exceed these exposure levels and the margin is very narrow for large groups. Therefore, measures should be taken to reduce cadmium exposure in the general population in order to minimize the risk of adverse health effects. The general population is primarily exposed to mercury via food, fish being a major source of methyl mercury exposure, and dental amalgam. The general population does not face a significant health risk from methyl mercury, although certain groups with high fish consumption may attain blood levels associated with a low risk of neurological damage to adults. Since there is a risk to the fetus in particular, pregnant women should avoid a high intake of certain fish, such as shark, swordfish and tuna; fish (such as pike, walleye and bass) taken from polluted fresh waters should especially be avoided. There has been a debate on the safety of dental amalgams and claims have been made that mercury from amalgam may cause a variety of diseases. However, there are no studies so far that have been able to show any associations between amalgam fillings and ill health. The general population is exposed to lead from air and food in roughly equal proportions. During the last century, lead emissions to ambient air have caused considerable pollution, mainly due to lead emissions from petrol. Children are particularly susceptible to lead exposure due to high gastrointestinal uptake and the permeable blood-brain barrier. Blood levels in children should be reduced below the levels so far considered acceptable, recent data indicating that there may be neurotoxic effects of lead at lower levels of exposure than previously anticipated. Although lead in petrol has dramatically decreased over the last decades, thereby reducing environmental exposure, phasing out any remaining uses of lead additives in motor fuels should be encouraged. The use of lead-based paints should be abandoned, and lead should not be used in food containers. In particular, the public should be aware of glazed food containers, which may leach lead into food. Exposure to arsenic is mainly via intake of food and drinking water, food being the most important source in most populations. Long-term exposure to arsenic in drinking-water is mainly related to increased risks of skin cancer, but also some other cancers, as well as other skin lesions such as hyperkeratosis and pigmentation changes. Occupational exposure to arsenic, primarily by inhalation, is causally associated with lung cancer. Clear exposure-response relationships and high risks have been observed.

Arsenic↗

Cytotoxicity and transcriptional activation of stress genes in human liver carcinoma cells (HepG2) exposed to cadmium chloride.

Epidemiological studies have shown that there exists some correlation between cadmium exposure and human cancers. The evidence that cadmium and cadmium compounds are probable human carcinogens is also supported by experimental studies reporting induction of malignant tumors formation in multiple species of laboratory animals exposed to these compounds. In vitro studies with mammalian cells have also shown that cadmium is clastogenic, but its mutagenic potential is rather weak. In this research, we performed the MTT assay for cell viability to assess the cytotoxicity of cadmium chloride (CdCl2), and the CAT-Tox (L) assay to measure the induction of stress genes in thirteen different recombinant cell lines generated from human liver carcinoma cells (HepG2), by creating stable transfectants of different mammalian promoter-chloramphenicol acetyltransferase (CAT) gene fusions. Cytotoxicity experiments with the parental cell line yielded a LC50 of 6.1 +/- 0.8 microg/mL, upon 48 h of exposure. Four (metallothionein--HMTIIA, 70-kDa heat shock protein--HSP70, xenobitic response element--XRE, and cyclic adenosine monophosphate response element--CRE) out of the 13 constructs evaluated showed statistically significant inductions (p < 0.05). The induction of these genes was concentration-dependent. Marginal inductions were also recorded for the c-fos, and 153-kDa growth arrest DNA damage (GADD153) promoters, indicating a potential for CdCl2 to damage DNA. However, no significant inductions (p > 0.05) of gene expression were recorded for cytochrome P4501A1--CYP1A1, glutathion-S-transferase Ya subunit--GST Ya, nuclear factor kappa (B site) response element--NFkappaBRE, tumor suppressor protein response element--p53RE, 45-kDa growth arrest DNA damage--GADD45, 78-kDa glucose regulated protein--GRP78, and retinoic acid response element--RARE. As expected, these results indicate that metallothioneins and heat shock proteins appear to be excellent candidates for biomarkers for detecting cadmium-induced proteotoxic effects at the molecular and cellular levels. Induction of XRE indicates the potential involvement of CdCl2 in the biotransformation process in the liver, while activation of CRE indicates stimulation of cellular signaling through the protein kinases pathway.

Antineoplastic Agents↗

Genetic variation in the susceptibility to mercury and other metal compounds in Drosophila melanogaster.

The tolerance of Drosophila melanogaster to heavy metal compounds was investigated with special emphasis on methylmercury. A pronounced variation in tolerance to CH3HgOH, HgCl2, (C2H5)3PbCl, (CH3)3SnCl, and CdCl2 was recorded between 12 wild-type strains. After ranking the tolerance of the strains with respect to the five compounds rank correlations for experiments within and between compounds were calculated. The results showed a high degree of correlation within compounds but no unequivocal indication of a correlation between compounds, indicating that different mechanisms of genetic control for tolerance were operating for the five compounds. Rank correlations for experiments with 12 different mercury, lead, tin, and cadmium compounds and the same 12 wild-type strains only indicated one significant correlated response, between tripropyltin and tributyltin. A selection experiment for tolerance to methylmercury was performed with a foundation population, synthesized from four wild-type strains, showing a high initial tolerance. One control and two levels of treatment doses were used. A distinct selection response was obtained and a high tolerance was reached particularly for the high-dose selection line after 12 generations, when the experiment ended. Genetic analysis of the tolerance indicated a dominant and polygenic inheritance. Investigation of the uptake and excretion of CH3Hg203OH showed that the level of tolerance to methylmercury was correlated with the uptake of the mercury but apparently not with the rate of excretion. Cystein increased the susceptibility to methylmercury. Inorganic mercury and trimethyl lead exhibited a synergistic toxic effect, evidently as the result of an in vitro transmethylation of mercury. A high somatic susceptibility to methylmercury also applied to the induction of nondisjunction and sex-linked recessive lethals.

Animals↗

[Determination of cadmium binding proteins in the edible mushroom (Agaricus arvensis Schff, ex Fr.) (author's transl)].

The isolation and characterization of cadmium compounds from Agaricus arvensis Schff. ex Fr. are described. These compounds were extractable with buffers. Ultrafiltrations and protein precipitations suggested protein bound cadmium. The mushroom proteins were separated by gel chromatography and the cadmium content in the corresponding fractions was determined by flameless atomic absorption. Two cadmium containing protein fractions were found with cadmium concentrations of 2.1 and 1 mg/g protein, respectively. The molecular weights of both cadmium containing proteins were estimated to be about 2,000 and 15,000--20,000, respectively by comparison with standard proteins.

Agaricales↗

Pulmonary carcinogenicity of cadmium by inhalation in animals.

Although, the tumorigenic effect of cadmium after subcutaneous and intramuscular injection has been known since 1961, lung tumours after inhalation exposure were reported only more than 20 years later by Takenaka et al. (1983), using cadmium chloride aerosols. Based on these results, aerosols of cadmium sulfate, cadmium oxide and cadmium sulfide pigment were investigated for carcinogenic effects after inhalation exposure in rats, hamsters and mice. All the cadmium compounds tested appeared to have a very similar carcinogenic potency in the rat lung, whereas no exposure-related tumours occurred in hamsters and in mice only cadmium oxide seemed to increase the lung tumour rate. Subsequent analytical investigations of the aqueous suspension of cadmium sulfide used to generate the aerosol showed that it was soluble in water to some extent as a result of photo-oxidation. The exposure atmosphere therefore actually consisted of a mixture of sulfide and sulfate, and the observed lung tumour rate must be attributed to a combined action of the two compounds. For this reason, a clear-cut carcinogenic effect of cadmium sulfide could not be proved by this inhalation study, but because of the high carcinogenic potency of cadmium ions in the rat lung and because cadmium sulfide retained in the lung is bioavailable to a certain extent, aerosols of this compound should be regarded as a probable human carcinogen.

Administration, Inhalation↗

Cadmium carcinogenesis.

Cadmium is a heavy metal of considerable environmental and occupational concern. Cadmium compounds are classified as human carcinogens by several regulatory agencies. The most convincing data that cadmium is carcinogenic in humans comes from studies indicating occupational cadmium exposure is associated with lung cancer. Cadmium exposure has also been linked to human prostate and renal cancer, although this linkage is weaker than for lung cancer. Other target sites of cadmium carcinogenesis in humans, such as liver, pancreas and stomach, are considered equivocal. In animals, cadmium effectively induces cancers at multiple sites and by various routes. Cadmium inhalation in rats induces pulmonary adenocarcinomas, in accord with its role in human lung cancer. Cadmium can induce tumors and/or preneoplastic lesions within the rat prostate after ingestion or injection. At relatively high doses, cadmium induces benign testicular tumors in rats, but these appear to be due to early toxic lesions and loss of testicular function, rather than from a specific carcinogenic effect of cadmium. Like many other metals, cadmium salts will induce mesenchymal tumors at the site of subcutaneous (s.c.) or intramuscular (i.m.) injections, but the human relevance of these is dubious. Other targets of cadmium in rodents include the liver, adrenal, pancreas, pituitary, and hematopoietic system. With the exception of testicular tumors in rodents, the mechanisms of cadmium carcinogenesis are poorly defined. Cadmium can cause any number of molecular lesions that would be relevant to oncogenesis in various cellular model systems. Most studies indicate cadmium is poorly mutagenic and probably acts through indirect or epigenetic mechanisms, potentially including aberrant activation of oncogenes and suppression of apoptosis.

Animals↗

The possibility of food contamination with cadmium by means of coloured plastics.

By using spectrophotometric atomic absorption, the release of cadmium from some plastic materials (polyethylenes, PVC, polystyrene) used for manufacturing containers, wraps and household objects (which are coloured with pigments derived from cadmium compounds) was studied. Subchronic experiments (45 days) were carried out in white Wistar rats with extracts from cadmium-containing plastic in comparison with the pigment alone. The excreted cadmium in urine and the activity of some serum enzymes were determined. Histopathological changes of the main internal organs were observed. It was found that some pigments of the Papion type have the property of releasing cadmium in amounts exceeding the admitted sanitary levels, amounts which proved to be toxic, producing enzymic and histopathological changes in kidneys and testes.

Acetates↗

Mutagenicity of cadmium in mammalian cells: implication of oxidative DNA damage.

Cadmium and cadmium compounds are well established human carcinogens and are ubiquitously present in the environment. The carcinogenic mechanism(s) of cadmium remains largely unknown since direct mutagenic effect is weak in bacterial and in standard mammalian cell mutation assays. In this study, we show that when evaluated using the human-hamster hybrid A(L) cell mutation assay in which both intragenic and multilocus deletions can readily be detected, CdCl(2) is a strong mutagen that induces predominantly large deletion mutations. Concurrent treatment of A(L) cells with the oxyradical scavenger dimethyl sulfoxide significantly reduced the number of cadmium-induced mutations. In contrast, pre-treatment of cells with buthionine sulfoximine that depletes intracellular glutathione, increased cytotoxicity and mutagenicity of cadmium. These results demonstrate that reactive oxygen species mediate cadmium induced mutations in A(L) cells. With laser scanning confocal microscopy and the fluorescent probe 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, we demonstrated that cadmium induced a dose and time dependent formation of intracellular oxyradicals. Using immunoperoxidase staining coupled with a monoclonal antibody-specific for 8-OHdG adducts in DNA, we demonstrated that cadmium induced a dose dependent increase of 8-OHdG adducts, which accumulated with prolonged exposure. Furthermore, we showed that at low concentration, cadmium, attenuated removal of hydrogen peroxide induced 8-OHdG adducts. Thus, the carcinogenicity of cadmium can, in part, be explained by its mutagenic activity, which is mediated by reactive oxygen species induced DNA damage and by its interference with the repair of oxidative DNA damage.

Animals↗