04 August 2008

Chromium 6: A Killer Compound With An Improbable Trigger


Chromium 6, the cancer-causing compound that sparked the legal crusade by Erin Brockovich,
can be toxic in tiny doses. Brown University scientists have uncovered the unlikely culprit: vitamin C. In new research, the Brown team shows that when vitamin C reacts with even low doses of chromium 6 inside human cells, it creates high levels of cancer-causing DNA damage and mutations.

PROVIDENCE, R.I. [Brown University] - Even miniscule amounts of chromium 6 can cause cancer. Blame that do-gooder nutrient, vitamin C.

Brown University researchers have discovered that naturally occurring vitamin C reacts inside human lung cells with chromium 6, or hexavalent chromium, and causes massive DNA damage. Low doses of chromium 6, combined with vitamin C, produce up to 15 times as many chromosomal breaks and up to 10 times more mutations - forms of genetic damage that lead to cancer - compared with cells that lacked vitamin C altogether.

This finding is startling, said Anatoly Zhitkovich, an associate professor of medical science at Brown who oversaw the experiments. Outside cells, Zhitkovich said, vitamin C actually protects against the cellular damage caused by hexavalent chromium, the toxic chemical that starred as the villain in the true-to-life Hollywood drama, Erin Brockovich. In fact, vitamin C has been used as an antidote in industrial accidents and other instances when large amounts of chromium are ingested.

Vitamin C works protective wonders because it is a powerful antioxidant, blocking cellular damage from free radicals. Specifically, the vitamin rapidly "reduces," or adds electrons, to free radicals, converting them into harmless molecules. This electron transfer from vitamin C to chromium 6 produces chromium 3, a form of the compound that is unable to enter cells.

But what happens when chromium and vitamin C come together inside cells? Because vitamin C isn't found in cells grown in a lab, Zhitkovich and his team conducted
experiments using human lung cells supplemented with vitamin C. They learned that when vitamin C is present, chromium reduction has a very different effect. Cellular vitamin C acted as a potent toxic amplifier, sparking significantly more chromosomal breaks and cellular mutations.

"When we increased the concentration of vitamin C inside cells, we saw progressively more mutations and DNA breaks,
showing how seemingly innocuous amounts of chromium can become toxic," Zhitkovich said. "For years, scientists have wondered why exposure to small amounts of hexavalent chromium can cause such high rates of cancer. Now we know. It's vitamin C."

Hexavalent chromium is used to plate metals and to make paints, dyes, plastics and inks.
As an anticorrosive agent, it is also added to stainless steel, which releases hexavalent chromium during welding. Hexavalent chromium causes lung cancer and is found in 40 percent of Superfund sites nationwide. This is the toxic metal, found in drinking water in a small California town, that Erin Brockovich campaigned against, successfully winning residents a record settlement of $333 million in 1996.

Zhitkovich said his team's research, published in Nucleic Acids Research, might have policy implications.
When combined with vitamin C, chromium 6 caused genetic damage in cells in doses four times lower than current federal standards, Zhitkovich said. If additional research backs these findings, he said federal regulators might want to lower exposure standards.

Zhitkovich is part of a major Brown research initiative, the Superfund Basic Research Program, which addresses the health and environmental concerns created by hazardous waste contamination. As part of this program, funded by the National Institute of Environmental Health Sciences, Zhitkovich is conducting basic research that may result in a medical test that assesses DNA damage from hexavalent chromium. Former Brown graduate student Mindy Reynolds was lead author of the journal article. Brown research assistant Lauren Stoddard and postdoctoral research associate Ivan Bespalov also took part in the research. The National Institutes of Health funded the work.

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