Vitamin C produces gene-damaging compounds, test-tube study in Science reports

June 14, 2001

Vitamin C, known to be a DNA-protecting "antioxidant," is a switch hitter, also capable of inducing the production of DNA-damaging compounds, suggests a study in the 15 June issue of the international journal, Science. Mutations caused by these compounds have been found in a variety of tumors.

Such mutations can be repaired, however, and lead author Ian Blair of the Center for Cancer Pharmacology, at the University of Pennsylvania, cautioned that the study shouldn't be interpreted as a claim that vitamin C causes cancer. Nor does it question the wisdom of eating a balanced diet rich in fruits, vegetables, and whole grains, he said.

The findings, which come from test-tube experiments (in vitro), may help explain why vitamin C has thus far shown little effectiveness at preventing cancer in clinical trials, according to the Science authors.

"It's possible that vitamin C isn't working in cancer prevention studies because it's causing as much damage as it's preventing, but that's really speculation at this point. What we can say is that vitamin C clearly doesn't work when you expect it to, and now we're in a position to see if that's what's happening in vivo, [or, in living cells]" Blair said.

Some scientists have long recommended dietary supplements of vitamin C, particularly for treating and preventing cancer. But the supplements' effectiveness has been hotly debated, with critics saying they either have no effect or that they may be harmful.

"The logic being used [for vitamin C supplements] is that 'fruits, vegetables, etc. contain vitamin C; these foods prevent cancer; thus vitamin C prevents cancer," Blair said. "But our message is that it's the total diet that's important, not just one antioxidant in isolation."

Vitamin C is known to do beneficial work in the body, including acting as an antioxidant that "disarms" free radicals. These highly reactive ions are produced by the breakdown of oxygen, which occurs constantly in cells.

In addition to damaging DNA directly, free radicals can also act indirectly. They begin by converting linoleic acid, the major polyunsaturated fatty acid in sunflower, grape, and safflower cooking oils, as well as the major polyunsaturated fatty acid in human plasma, into another compound called a lipid hydroperoxide. When certain metal ions are present to act as catalysts, the lipid hydroperoxides degrade further, into DNA-damaging agents called "genotoxins."

These compounds react with DNA, switching one base for another in mutations that have been found in human tumors.

Scientists, including Blair and his colleagues, have suspected that vitamin C might also be capable of making lipid hydroperoxides degrade into genotoxins, in place of the transition metal ions.

To investigate, the Science authors added vitamin C to solutions of lipid hydroperoxides in the lab. They used concentrations comparable to those found in the human body, assuming a person would take 200 milligrams a day.

The vitamin was more than twice as efficient as transition metal ions at inducing the formation of genotoxins, including a particularly potent variety.

The researchers' next step is to see whether vitamin C produces significant amounts of genotoxins in intact cells, and whether they generate cancer-causing mutations.
-end-
The other members of the research team are Seon Hwa Lee and Tomoyuki Oe, of the Center for Cancer Pharmacology, at the University of Pennsylvania. Funding for this research was provided by the National Cancer Institute and the University of Pennsylvania Cancer Center.

American Association for the Advancement of Science

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