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An early diagnostic biomarker for breast cancer is essential to improve outcome. High precision isotopic analysis, originating in Earth sciences, can detect very small shifts in metal pathways. For the first time, the natural intrinsic Zn isotopic compositions of various tissues in breast cancer patients and controls were determined. Breast cancer tumours were found to have a significantly lighter Zn isotopic composition than the blood, serum and healthy breast tissue in both groups. The Zn isotopic lightness in tumours suggests that sulphur rich metallothionein dominates the isotopic selectivity of a breast tissue cell, rather than Zn-specific proteins. This reveals a possible mechanism of Zn delivery to Zn-sequestering vesicles by metallothionein, and is supported by a similar signature observed in the copper isotopic compositions of one breast cancer patient. This change in intrinsic isotopic compositions due to cancer has the potential to provide a novel early biomarker for breast cancer.

In response to new European Union regulations, studies are underway to mitigate accumulation of toxic cadmium (Cd) in cacao (Theobroma cacao, Tc). This study advances such research with Cd isotope analyses of 19 genetically diverse cacao clones and yeast transformed to express cacao natural resistance-associated macrophage protein (NRAMP5) and heavy metal ATPases (HMAs). The plants were enriched in light Cd isotopes relative to the hydroponic solution with Δ 114/110 Cd tot-sol = −0.22 ± 0.08‰. Leaves show a systematic enrichment of isotopically heavy Cd relative to total plants, in accord with closed-system isotope fractionation of Δ 114/110 Cd seq-mob = −0.13‰, by sequestering isotopically light Cd in roots/stems and mobilisation of remaining Cd to leaves. The findings demonstrate that (i) transfer of Cd between roots and leaves is primarily unidirectional; (ii) different clones utilise similar pathways for Cd sequestration, which differ from those of other studied plants; (iii) clones differ in their efficiency of Cd sequestration. Transgenic yeast that expresses TcNRAMP5 (T. cacao natural resistance-associated macrophage gene) had isotopically lighter Cd than did cacao. This suggests that NRAMP5 transporters constitute an important pathway for uptake of Cd by cacao. Cd isotope signatures of transgenic yeast expressing HMA-family proteins suggest that they may contribute to Cd sequestration. The data are the first to record isotope fractionation induced by transporter proteins in vivo.

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This study reports spatial and temporal variability of Zn and Cu isotopes in atmospheric particulate matter (PM) collected in two major European cities with contrasting atmospheric pollution, Barcelona and London. We demonstrate that nontraditional stable isotopes identify source contributions of Zn and Cu and can play a major role in future air quality studies. In Barcelona, samples of fine PM were collected at street level at sites with variable traffic density. The isotopic signatures ranged between −0.13 ± 0.09 and −0.51 ± 0.05‰ for δ 66 Zn IRMM and between +0.04 ± 0.20 and +0.33 ± 0.15‰ for δ 65 Cu AE633 .Copper isotope signatures similar to those of Cu sulfides and Cu/ Sb ratios within the range typically found in brake wear suggest that nonexhaust emissions from vehicles are dominant. Negative Zn isotopic signatures characteristic for gaseous emissions from smelting and combustion and large enrichments of Zn and Cd suggest contribution from metallurgical industries. In London, samples of coarse PM collected on the top of a building over 18 months display isotope signatures ranging between +0.03 ± 0.04 and +0.49 ± 0.02‰ for δ 66 Zn IRMM and between +0.37 ± 0.17 and +0.97 ± 0.21‰ for δ 65 Cu AE633 . Heavy Cu isotope signatures (up to +0.97 ± 0.21‰) and higher enrichments and Cu/Sb ratios during winter time indicate important contribution from fossil fuel combustion. The positive δ 66 Zn IRMM signatures are in good agreement with signatures characteristic for ore concentrates used for the production of tires and galvanized materials, suggesting nonexhaust emissions from vehicles as the main source of Zn pollution.