Biological Trace Element Research

The subcutaneous injection of Walker 256 carcinosarcoma cells into a rat was followed by a pronounced increase in plasma ceruloplasmin activity. This lasted only about 3 weeks even though the tumors were still enlarging rapidly. Based upon studies with67Cu, the increase in plasma ceruloplasmin seemed to reflect increased production of the enzyme by the livers of rats bearing the tumors. Injections of turpentine also raised plasma ceruloplasmin, but to a significantly lesser extent and normal values were reached within 2 weeks.

Breast cancer incidence in Nigerian women has significantly increased during the past three decades in parallel with the rapid industrialization of that country. This suggested that the associated widespread contamination of the soil and of the water supplies by lead (Pb) and other industrial metals was a major contributing cause. Because of its many domestic, industrial, and automotive uses, Pb is of particular concern as it has been shown to promote the development of mammary tumors in murine mammary tumor virus-infected female C3H mice at levels as low of 0.5 ppm Pb in the drinking water. Lead belongs to the group of selenium-antagonistic elements that interact with selenium (Se), abolishing its anti-carcinogenic effect. Lead on chronic, low-level exposure in addition also accelerates tumor growth rates. Higher levels of Pb were found in blood and head hair samples of newly diagnosed patients with breast cancer, all with infiltrating ductal carcinoma, the most common form of breast cancer in Nigeria, seen at Obafemi Awolowo University, than in cancer-free controls from the same area. Evidence for interactions between Pb and Se was obtained from blood, hair, and tumor biopsy tissue analyses. Furthermore, the Pb levels in hair samples of the patients were directly correlated with the volumes of their tumors, in accord with the tumor growth-promoting effects of Pb. Conversely, Se levels in hair and blood were inversely correlated with the tumor volumes, consistent with the anti-proliferative effects of Se. Several other elements, e.g., Cd, Hg, Cr, Sn, and As, were detected in the scalp hair of the patients and the controls, although at significantly lower levels than those of Pb. However, correlation calculations revealed them also to interact with Se, suggesting that only a fraction of the Se in organs and tissues is actually present in bioactive forms. In metal-exposed subjects, a state of latent Se deficiency may exist, resulting in depressed immune functions and increased cancer susceptibility. Evidence is presented to show that Pb and other metals also interact with iodine, another vitally important essential trace element believed to protect against breast cancer development. Public health programs aiming at lowering the breast cancer risk of Nigerian women thus will have to include effective measures to protect the population from exposures to Pb and other industrial metals that are presently contaminating the environment and the water supplies.

Selenium (Se) has been demonstrated in previous studies to inhibit mammary tumorigenesis in C3H mice infected with the murine mammary tumorvirus, MMTV. The antitumorigenic effects of Se in this animal model of breast cancer were subsequently shown to be counteracted by Se-antagonistic elements. Lead (Pb), for example, was found to abolish the anticarcinogenic effects of Se at 5 ppm in the drinking water. The present study was undertaken to explore the effects of Pb at just 0.5 ppm in the water, i.e., at a level comparable to the concentrations of Pb that have been measured in the tap water of older homes in some communities. Groups of 30 female virgin C3H/St mice infected with MMTV maintained on Torula yeast-based diets containing either 0.15 or 0.65 ppm of yeast-based organic Se and received either deionized water or water containing 0.5 ppm Pb as the acetate over their entire postweaning lifespan. In the control group on deionized water and the 0.15 ppm Se feed, the tumor incidence was 78.6%, which is normal for this strain. Increasing the Se content of the feed to 0.65 ppm lowered the tumor incidence to 30%, demonstrating the antitumorigenic effect of Se. In the experimental groups, the Pb-exposed mice on the 0.15 ppm Se feed developed signs of chronic Pb toxicity as evidenced by diminished weight gain that persisted up to the age of 10 months, during which period the animals remained tumor-free. Thereafter, weight gains ensued to near the values of the controls, and the tumors began to develop in rapid succession until the final tumor incidence of 73.7% was reached. In the group of mice on the 0.65 ppm Se feed, the toxic effects of Pb were diminished, as evidenced by the normal weight gains during the first 10 months but with concomitant physiological inactivation of Se, causing 82.6% of the mice to develop tumors, with the first tumor to appear at the age of 5 months, 7 months earlier than in the Pb-unexposed controls. In addition, tumor growth rates in this group were greatly accelerated and the survival of the tumor-bearing animals was significantly shortened. Direct evidence for the interactions of Pb with Se were obtained by determinations of the two elements in the livers, kidneys, and hair of tumor-free and tumor-bearing mice. However, the exposure of the mice to Pb in the water also altered the levels of Zn, Cu, Fe, and Cr in the organs and tissues, more so in tumor-bearing than tumor-free animals. The present study demonstrates the need to consider the interactions of Se with other trace elements in discussions of its mechanism of anticarcinogenic action.

The interactions between Hg2+, Ce3+, and the mixuure of Ce3+ and Hg2+, and DNA from fish intestine in vitro were investigated by using absorption spectrum and fluorescence emission spectrum. The ultraviolet absorption spectra indicated that the addition of Hg2+, Ce3+, and the mixture of Ce3+ and Hg2+ to DNA generated an obviously hypochromic effect. Meanwhile, the peak of DNA at 205.2 nm blue-shifted and at 258.2 nm red-shifted. The size of the hypochromic effect and the peak shift of DNA by metal ion treatments was Hg2+>Hg2++Ce3+>Ce3+. The fluorescence emission spectra showed that with the addition of Hg2+, Ce3+, and the mixture of Ce3+ and Hg2+ the emission peak at about 416.2 nm of DNA did not obviously change, but the intensity reduced gradually and the sequence was Hg2+>Hg2++Ce2+>Ce3+. Hg2+, Ce3+, and the mixture of Ce3+ and Hg2+ had 1.12, 0.19, and 0.41 binding sites to DNA, respectively; the fluorescence quenching of DNA caused by the metal ions all attributed to static quenching. The binding constants (K A ) of binding siees were 8.98×104 L/mol and 1.02×104 L/mol, 5.12×104 L/mol and 1.10×103 L/mol, 6.66×104 L/mol and 2.36×103 L/mol, respectively. The results showed that Ce3+ could relieve the destruction of Hg2+ on the DNA structure.

In order to assess the environmental risks associated with the emission of fly-ash into the atmosphere and its storage on waste heaps, the trace element contents of fly-ashes from burning Polish hard coal were determined by a newly developed INAA method. Leaching of trace elements from the fly-ash by water and H2SO4 solution (pH≈2.5) simulating acid rain, respectively, was studied using AAS and spectrophotometric methods. Analogous experiments were done with neutron-irradiated fly-ash, following the composition of the eluate gamma-spectrometrically. The new fine fly-ash (CTA-FFA-1) candidate reference material was prepared, and the certification was undertaken on the basis of an international intercomparison run. Preliminary evaluation of results shows that at least 38 elements will be certified and, in addition, the “information values” for at least 12 elements will be given.