Unit of Metals & Health

The aim of our research is to identify toxic effects of metals, and further, to understand causal relationships between metal exposure and various diseases, and how susceptibility factors influence these relationships.

Exposure to toxic metals, such as arsenic, cadmium, mercury, and lead, are major threats to public health, globally as well as in Sweden. Exposure often occurs via drinking water and/or food. The unit has for many years been world-leading in research on arsenic and cadmium. Today our research primarily concerns metals with major impact on public health, and for which there still are gaps in knowledge, i.e. for arsenic, cadmium, manganese, lithium, and boron. We also elucidate the importance of essential elements such as iron, zinc, and selenium, as they may interact with toxic metals. A majority of our research is focused on health effects of metal exposure early in life, a particularly sensitive period to toxic insults.

We study mechanisms of metal toxicity, especially oxidative stress, epigenetic and hormone-related changes. Many toxic metals, such as arsenic, cadmium, and lead, cause oxidative stress. Recent research suggests that metals can interfere with epigenetic processes, which may make some metals carcinogenic, although they appear not to be strongly mutagenic. Moreover, epigenetic interference can explain why exposure to metals early in life seem to cause diseases later in life. Several of the metals are endocrine disruptors, particularly cadmium, but the hormone systems affected are still to be identified.

There are large individual differences in susceptibility to metal toxicity and we evaluate sensitivity factors such as gender, nutritional status, and genetics. For example, studies have shown that women generally have higher levels of cadmium in their bodies than men. Genetics seems to play a significant role for metal susceptibility. One of the clearest examples of gene-environment interaction is the gene AS3MT, which we have shown to strongly affect the metabolism and sensitivity to arsenic in the body.

The unit collaborates with many research groups, both in Sweden and elsewhere, e.g., in studies concerning metal exposure around the Mediterranean Sea, in the Seychelles, Bangladesh, and the Andes Mountains. Successful research in this area requires sensitive and specific analysis of specific biomarkers of exposure and early effects. Our exposure measurements are largely based on analyzes by ICP-MS. For speciation of arsenic metabolites, we use HPLC on-line with ICP-MS. The laboratory also has expertise, instruments and methods for analysis of genetic damage, by determination of telomere length, gene expression, and epigenetic changes, including DNA methylation and microRNAs. Further, the laboratory performs genotyping of various types of polymorphisms.

Researchers at the unit participate in health risk assessments, particularly for the EFSA, the Swedish National Food Administration, the Swedish Chemicals Agency, and the American Academy of Sciences. Our research has, for example, been crucial for the risk assessment of arsenic and cadmium performed by EFSA, the American Academy of Sciences, and the US EPA.

Funding

Swedish Research Council
Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS)
Swedish Research Council for Health, Working Life and Welfare (FORTE)
AFA Insurance
Sida (via Swedish Research Council)
National Institute of Health, U.S.A.

Ongoing projects

Metallomics laboratory

The metallomics laboratory performs measurements of toxic and essential trace elements, primarily through various exposure biomarkers, often within large epidemiological studies (high-throughput). It has been developed and implemented since more than 30 years at the unit of Metals and Health, and has generated hundreds of original scientific publications. It is primarily a research laboratory, but we may also carry out analyses on request, particularly from other research groups, the health sector and Swedish authorities.

In the metallomics laboratory, we measure metals and other elements in biological fluids (e.g. urine, blood and breast milk), tissues (whole tissue samples, specific cells and cellular constituents), and as well as environmental samples (e.g. water, food and particles), using highly sensitive ICP-MS instruments in clean-room facility. Our instruments include one Agilent one Agilent 7700x and one Agilent 7900, both quadrupole ICP-MS with collision/reaction cell technology. They are easy to connect to HPLC (Agilent 1100x) for pre-separation of e.g. different metabolites. To enable ICP-MS analysis of samples with more complex matrices, foremost solid samples, these are first digested in a Milestone UltraCLAVE II microwave digestion system. More information about the metallomics laboratory.