Cadmium Studies Suggest New Pathway To Human Cancer

["Bruce Manninen" <bmanninen@SEC-TN.COM>]

This article, though not radiological, should interest RADSAFE subscribers.

This is from Science Daily:



 http://www.sciencedaily.com/releases/2003/06/030609010937.htm



Researchers at the National Institute of Environmental Health Sciences today

reported that cadmium – a naturally occurring metal which shows up in food,

water and cigarette smoke – disturbs a DNA repair system that is important

in preventing cancer. "Unless cadmium is unique in its mechanism," NIEHS'

Dmitry A. Gordenin, Ph.D., said, "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." Dr. Gordenin is the senior author on the paper which he and his

colleagues report in today's online issue of the journal Nature Genetics.

The report will appear in the print version of the journal in July.



A naturally present white metal, cadmium already is listed in the federal

Report on Human Carcinogens as a "known human carcinogen" and has long been

known to cause human lung cancer in cadmium-related industry if safeguards

are not taken. The new studies, in yeast and human cells, are intended to

show how this happens.



Soon after the discovery of the DNA double helix 50 years ago, studies

showed environmental chemicals and stresses could cause mutations in the DNA

that could result in uncontrolled cell growth, leading to cancer. But the

NIEHS group's new contribution is to show that cadmium causes mutations in

another way – by inhibiting the ability of cells to repair routine errors

made when the DNA is copied to make new cells.



Without the repairs, cells mutate "dramatically" and multiply.



The studies 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, like humans. And the researchers

said that their studies with extracts of human cells and initial studies in

cultured human cells also suggest a similar mechanism.



Dr. Gordenin said, "Cells must duplicate their DNA in order to increase

their numbers enough to replace dying cells. However, in duplicating the DNA

mistakes are made with a frequency that organisms would not be able to

tolerate, if uncorrected. Luckily, most organisms do correct these mistakes

by efficient mechanisms akin to a computer's 'spellcheck.' One of these

correctives is post-replication mismatch repair. 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.



"What we have shown," Dr. Gordenin continued, "is that environmental factors

such as cadmium can cause high levels of mutations not only by damaging DNA

directly but also by inhibiting DNA repair."



Michael A. Resnick, Ph.D., an NIEHS senior scientist and a co-author of the

report, said, "What cadmium exposure does in living cells is to block

post-replication mismatch repair of natural errors and thus increase the

mutations dramatically – as much as 2,000 fold. Genetically, this can result

in a vast increase in errors that could be catastrophic."



Thomas A. Kunkel, Ph.D., another NIEHS senior scientist on the project, said

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."



Cadmium is a natural element in the earth, found in all soils and rocks,

including coal and fertilizers. It is used in metal coatings, plastics and

batteries, partly because it does not corrode easily. Although workers in

these industries may be exposed to greater concentrations, 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.



Until 1997, cadmium carbonate and cadmium chloride were used as fungicides

for golf courses and home lawns.



Cadmium disappears from organisms very slowly. Its half-life in the human

body can be as long as 20 years.



Yong Hwan Jin, Ph.D., is the first author on the study report today. Other

co-authors are Alan B. Clark, Robbert (sic) J.C. Slebos, Ph.D., Hanan

Al-Refai and Jack A Taylor, Ph.D. Dr. Taylor is with both the NIEHS

Laboratory of Moledular Carcinogenesis and the Epidemiology Branch. The

other scientists are with the Laboratory of Molecular Genetics.



The National Institute of Environmental Health Sciences is an institute of

the federal National Institutes of Health within the Department of Health

and Human Services. NIEHS' laboratories are in Research Triangle Park, a

science enclave between Raleigh, Durham and Chapel Hill, N.C. The National

Toxicology Program, which produces the federal government's Report on

Carcinogens – the list of known and reasonably anticipated human carcinogens

referred to in paragraph two – is headquartered at the NIEHS.





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This story has been adapted from a news release issued by NIH/National

Institute Of Environmental Health Sciences.



Bruce Manninen, CHP

bmanninen@sec-tn.com



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