At the cellular level, cadmium (Cd) induces both damaging and repair processes in which the cellular redox status plays a crucial role. Being not redox-active, Cd is unable to generate reactive oxygen species (ROS) directly, but Cd-induced oxidative stress is a common phenomenon observed in multiple studies. The current review gives an overview on Cd-induced ROS production and anti-oxidative defense in organisms under different Cd regimes. Moreover, the Cd-induced oxidative challenge is discussed with a focus on damage and signaling as downstream responses. Gathering these data, it was clear that oxidative stress related responses are affected during Cd stress, but the apparent discrepancies observed in between the different studies points towards the necessity to increase our knowledge on the spatial and temporal ROS signature under Cd stress. This information is essential in order to reveal the exact role of Cd-induced oxidative stress in the modulation of downstream responses under a diverse array of conditions.

Accurate quantification by real-time RT-PCR relies on normalisation of the measured gene expression data. Normalisation with multiple reference genes is becoming the standard, but the best reference genes for gene expression studies within one organism may depend on the applied treatments or the organs and tissues studied. Ideally, reference genes should be evaluated in all experimental systems. A number of candidate reference genes for Arabidopsis have been proposed, which can be used as a starting point to evaluate their expression stability in individual experimental systems by available computer algorithms like geNorm and NormFinder. Using this approach, we identified the best three reference genes from a set of ten candidates -that included three traditional "housekeeping" genes -for normalisation of gene expression when roots and leaves of Arabidopsis thaliana are exposed to cadmium (Cd) and copper (Cu). The expression stabilities of AT5G15710 (F-box protein), AT2G28390 (SAND family protein), and AT5G08290 (mitosis protein YLS8) were the highest when considering the effect to the roots and shoots of Cd and Cu treatments. Even though the effect of Cd and excess Cu on the plants is very different, the same best reference genes were identified when considering Cd or Cu treatments separately. This suggests that these three genes may also be suitable when studying the gene expression after exposure of Arabidopsis thaliana to increased concentrations of other metals.

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We focus on the recent evidence that elucidates our understanding about the effects of cadmium (Cd) on human health and their prevention. Recently, there has been substantial progress in the exploration of the shape of the Cd concentrationresponse function on osteoporosis and mortality. Environmental exposure to Cd increases total mortality in a continuous fashion without evidence of a threshold, independently of kidney function and other classical factors associated with mortality including age, gender, smoking and social economic status. Pooled hazard rates of two recent environmental population based cohort studies revealed that for each doubling of urinary Cd concentration, the relative risk for mortality increases with 17% (95% CI 4.2-33.1%; P \ 0.0001). Tubular kidney damage starts at urinary Cd concentrations ranging between 0.5 and 2 lg urinary Cd/g creatinine, and recent studies focusing on bone effects show increased risk of osteoporosis even at urinary Cd below 1 lg Cd/g creatinine. The non-smoking adult population has urinary Cd concentrations close to or higher than 0.5 lg Cd/g creatinine. To diminish the transfer of Cd from soil to plants for human consumption, the bioavailability of soil Cd for the plants should be reduced (external bioavailability) by maintaining agricultural and garden soils pH close to neutral (pH-H 2 O of 7.5; pH-KCL of 6.5). Reducing the systemic bioavailability of intestinal Cd can be best achieved by preserving a balanced iron status. The latter might especially be relevant in groups with a lower intake of iron, such as vegetarians, and women in reproductive phase of life. In exposed populations, house dust loaded with Cd is an additional relevant exposure route. In view of the insidious etiology of health effects associated with low dose exposure to Cd and the current European Cd intake which is close to the tolerable weekly intake, one should not underestimate the importance of the recent epidemiological evidence on Cd toxicity as to its medical and public health implications.

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Background: Studies emphasize the importance of particulate matter (PM) in the formation of reactive oxygen species and inflammation. We hypothesized that these processes can influence mitochondrial function of the placenta and fetus.Objective: We investigated the influence of PM10 exposure during pregnancy on the mitochondrial DNA content (mtDNA content) of the placenta and umbilical cord blood.Methods: DNA was extracted from placental tissue (n = 174) and umbilical cord leukocytes (n = 176). Relative mtDNA copy numbers (i.e., mtDNA content) were determined by real-time polymerase chain reaction. Multiple regression models were used to link mtDNA content and in utero exposure to PM10 over various time windows during pregnancy.Results: In multivariate-adjusted analysis, a 10-µg/m³ increase in PM10 exposure during the last month of pregnancy was associated with a 16.1% decrease [95% confidence interval (CI): –25.2, –6.0%, p = 0.003] in placental mtDNA content. The corresponding effect size for average PM10 exposure during the third trimester was 17.4% (95% CI: –31.8, –0.1%, p = 0.05). Furthermore, we found that each doubling in residential distance to major roads was associated with an increase in placental mtDNA content of 4.0% (95% CI: 0.4, 7.8%, p = 0.03). No association was found between cord blood mtDNA content and PM10 exposure.Conclusions: Prenatal PM10 exposure was associated with placental mitochondrial alterations, which may both reflect and intensify oxidative stress production. The potential health consequences of decreased placental mtDNA content in early life must be further elucidated.

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Over the years, anthropogenic factors have led to cadmium (Cd) accumulation in the environment causing various health problems in humans. Although Cd is not a Fenton-like metal, it induces oxidative stress in various animal models via indirect mechanisms. The degree of Cd-induced oxidative stress depends on the dose, duration and frequency of Cd exposure. Also the presence or absence of serum in experimental conditions, type of cells and their antioxidant capacity, as well as the speciation of Cd are important determinants. At the cellular level, the Cd-induced oxidative stress either leads to oxidative damage or activates signal transduction pathways to initiate defence responses. This balance is important on how different organ systems respond to Cd stress and ultimately define the pathological outcome. In this review, we highlight the Cd-induced oxidant/antioxidant status as well as the damage versus signalling scenario in relation to Cd toxicity. Emphasis is addressed to Cd-induced pathologies of major target organs, including a section on cell proliferation and carcinogenesis. Furthermore, attention is paid to Cd-induced oxidative stress in undifferentiated stem cells, which can provide information for future therapies in preventing Cd-induced pathologies.