Cadmium Disrupts Ability of Cells to Fight Cancer

RESEARCH TRIANGLE PARK, North Carolina, June 9, 2003 (ENS) - Cadmium, a naturally occurring metal found in food, water and cigarette smoke, disrupts a DNA repair system that is important in preventing cancer, according to researchers at the National Institute of Environmental Health Sciences (NIEHS). The metal, primarily used to make batteries, is a known human carcinogen and has long been known to cause human lung cancer in cadmium-related industries unless strict safeguards are taken.

But unlike most carcinogens that work by attacking DNA directly, the NIEHS study released today indicates that cadmium causes mutations in another way, explains the study's senior author Dr. Dmitry Gordenin.

The NIEHS research team showed that cadmium causes mutations by inhibiting the ability of cells to repair routine errors made when the DNA is copied to make new cells.

"Unless cadmium is unique in its mechanism, it would seem that environmental factors may cause genetic defects and cancer not only by attacking our DNA directly but also by undermining the mechanisms by which faulty DNA replication is repaired," Gordenin said.

Cadmium is a natural element and can be found in air, water, soil and food. (Photo courtesy Royal Society of Chemistry)

Without these corrective mechanisms, mutations would occur and multiply in cell after cell, which could lead to cancer, reproductive problems, birth defects or other ills.

The researchers found that cadmium blocks "post-replication mismatch repair" of natural errors.

This increases mutations "as much as 2,000 fold," said Dr. Michael Resnick, an NIEHS senior scientist and a co-author of the report.

"Genetically, this can result in a vast increase in errors that could be catastrophic," Resnick said.

The researchers say that the amount of cadmium needed to inhibit repair and increase mutations was remarkably small.

"We saw substantial effect from cadmium exposure from concentrations that may well be environmentally relevant especially to cadmium-related industry workers and smokers," said Dr. Thomas Kunkel, another NIEHS senior scientist who worked on the study.

Cadmium is a natural element, found in all soils and rocks, including coal and fertilizers. Its natural presence in air, water, soil and foodstuffs results mainly from mining and metal processing operations, gradual rock erosion and abrasion, as well as from volcanic eruptions.

Cadmium is not mined, rather it is a byproduct of the smelting of other metals such as zinc, lead and copper. The soft, silver-white metal has been used for metal coatings, and in paint, plastics and batteries, because it does not corrode easily, has a low melting point and excellent electrical conduction.

Scientists hope a better understanding of how carcinogens affect DNA will lead to improvements in defining at risk populations. (Photo courtesy National Institute of General Medical Sciences (NIGMS))

The primary health concerns are for industrial workers who may be exposed to generation concentrations, but the general population can be exposed to cadmium from breathing cigarette smoke, drinking contaminated water or eating foods that contain it. Smoking doubles the average daily intake.

Cadmium disappears from organisms very slowly and its half-life in the human body can be as long as 20 years.

Until banned by the EPA in 1997, cadmium carbonate and cadmium chloride were used as fungicides for golf courses and home lawns.

The NIEHS studies, reported in today's online issue of the journal "Nature Genetics," were done in yeast cells - the living cells used to make bread rise - which have proved a useful tool for studying cellular activities.

Previous work has demonstrated that what happens in yeast cells generally also happens in more complex life forms. The researchers say that their studies with extracts of human cells and initial studies in cultured human cells also suggest a similar mechanism to the one found in the study of yeast cells.