In vitro assessment of the toxicity of metal compounds

A review of in vitro mutagenesis assessment of metal compounds in mammalian and nonmammalian test systems has been compiled. Prokaryotic assays are ineffective or inconsistent in their detection of most metals as mutagens, with the notable exception of hexavalent chromium. Mammalian assay systems appear to be similarly inappropriate for the screening of metal compounds based upon the limited number of studies that have employed those compounds having known carcinogenic activity. Although of limited value as screening tests for the detection of potentially carcinogenic metal compounds, the well-characterized in vitro mutagenesis systems may prove to be of significant value as a means to elucidate mechanisms of metal genotoxicity.     

Simultaneous determination of Zn,Cd, Pb,and Cu in urine of patients with blackfoot disease using anodic stripping voltammetry

Blackfoot disease (BFD) is an endemic peripheral vascular disorder resulting in gangrene of the lower extremities, especially the feet, among residents in a limited area on the southwest coast of Taiwan. In the present study, the concentrations of zinc, cadmium, lead, and copper in urine of BFD patients with matched normal controls are investigated by differential pulse anodic stripping voltammetry (DPASV) on a hanging mercury drop electrode (HMDE). The analytical results indicate that urinary copper, cadmium, and lead of the BFD patients are significantly higher than those of the controls. In addition, the patients showed a significantly lower concentration of zinc in the urine than the normal controls. The possible connection of these elements with the etiology of the disease is discussed.     

Cadmium exposure of rainbow trout, Salmo gairdneri Richardson: effects on immune functions

Differential leucocyte counts, phagocytosis, humoral antibody response and the in vitro blasto-genetic response to mitogens (lipopolysaccharide and Concanavalin A) and to an antigen ( Vibrio anguillarum ) were studied in rainbow trout exposed to 0,0.7 or 3.6 μg Cd 1⁻¹ for 12 weeks.
Although the fish did not exhibit any clinical or histological changes, cadmium exposure was found to affect two of the immune parameters measured. The cellular response of fish immunized with V. anguillarum to the homologous antigen was significantly lower for splenocytes obtained from fish exposed to cadmium for 9 weeks (3.6 μg Cd 1⁻¹ group) than for splenocytes obtained from non-exposed fish. Conversely, the humoral antibody response to V. anguillarum O-antigen was higher in the 3.6 μg Cd 1⁻¹ group than in the non-exposed group. Protective immunity of fish vaccinated against V. anguillarum was equally as good in the cadmium-exposed group as in the non-exposed group. No cadmium-induced changes in differential leucocyte counts or in the proportions of phagocytic cells were observed.     

Effects of chelating agents on the cadmium burden of cells in culture

The effects of some new chelating agents on the cadmium burden of CHO cells in culture were investigated. The chelators were sodium-N-(4-methoxybenzyl)-D-glucamine-dithiocarbamate (MeOBG-DTC), sodium-N-benzyl-D-glucaminedithiocarbamate (BG-DTC) and di-isopropylmeso-2,3-dimercapto succinate (DiP-DMSA). The results were compared with the effect of the well known dimercaptopropanol (BAL).The derivates of dithiocarbamate are much less toxic than DiP-DMSA and BAL. All chelators effectively prevent Cd uptake into the cells. Mobilization of intracellular Cd, however, is more effective by the DTC-derivatives than by DiP-DMSA or BAL. Within the cell the major fraction of Cd after 48 hours incubation is found in the nuclei and cytosol and very little in the peroxisomes. The chelating agents remove the metal mostly from nuclei and cytosol. Incubation of the cells with cadmium leads to the induction of a Cd binding protein of an apparent molecular weight of 12500 Da, presumably metallothionein. MeOBG-DTC is more effective in removing the metal from this protein than BG-DTC.Abbreviations MeOBG-DTC Na-N(4-methoxybenzyl)-D-glucaminedithiocarbamate - BG-DTC Na-N-benzyl-D-glucaminedithiocarbamate - DiP-DMSA di-isopropyl-2,3-dimercaptosuccinate - BAL 2,3-dimercaptopropane-1-o1 - Da dalton - MEM minimum essential medium - IU international units - FBS fetal bovine serum - CD unbroken cells and debris - N nuclei - ML mitochondria, and lysosomes - P peroxisomes - HMW high molecular weight - MT metallothionein     

Association between blood cadmium level and bone mineral density reduction modified by renal function in young and middle-aged men

The association between cadmium exposure and bone mineral density (BMD) has not been well studied in young and middle-aged men. This study examined the relationship between the level of blood Cd (BCd) and BMD in a young to middle-aged representative male population while considering renal function. Using data from the 4th Korea National Health and Nutrition Examination Survey, 2008–2009, 1275 adult men aged 20–64 years were analyzed. BCd was measured by atomic absorption spectrophotometry and renal function was assessed by the estimated glomerular filtration rate (eGFR) with CKD-EPI formula. The risk of lower bone density was increased according to the increase in BCd levels after adjusting for eGFR and covariates, in which a significant interaction between BCd and eGFR existed. Significant negative associations between BCd and BMD were found: beta (p-value) were −0.03 (0.02), −0.04 (0.004) and −0.03 (0.04) in total femur, lumbar spine and femoral neck, respectively, which were limited to the people with eGFR ≤ lower 25%. Although, a causal relationship could not be determined because of a cross-sectional design in the present study, the results suggest low level Cd toxicity to bone via low eGFR and that measures to reduce environmental Cd exposure may be helpful to prevent bone loss in men.     

Incorporation of [35S]methionine in higher plants reveals that stimulation of the D1 reaction centre II protein turnover accompanies tolerance to heavy metal stress

The effects of cadmium stress (CdCl₂) on photochemical activity and protein behaviour of photosystem II (PSII) were studied in vivo and in vitro . Treatments of pea ( Pisum sativum ) and broad bean ( Vicia faba ) plants with 0·05–5 m M cadmium (CdCl₂) modified PSII activity with a resulting increase in electron transfer followed by an inhibition and damage to the oxygen-evolving complex. Pulse-chase experiments with [³⁵S]methionine in vivo followed by the separation of the radiolabelled thylakoids into grana and stroma exposed regions indicated that the synthesis, degradation and assembly of the D1 protein were greatly affected by cadmium. Initially D1 synthesis increased, later slowing down when the stress became advanced; at the same time the D1 degradation was increased. Binding studies with radiolabelled [¹⁴C]herbicide revealed that the Q_B pocket activity was also altered. However, the primary consequence of cadmium stress was the disassembly of the stacked regions. The measurements indicated differential tolerance to cadmium stress between the two plant species, which was not caused by either differential metal uptake or binding to the PSII complex. This suggests that the resulting changes in D1 turnover are a consequence of an unknown primary effect of cadmium on the PSII apparatus. However, we show that the higher tolerance to heavy metal stress found in broad bean plants relative to pea is accompanied by stimulation of D1 turnover. These experiments supported by previous data suggest that modulation of D1 turnover under stress is a commonly occurring process.