Tuesday, June 10, 2003

By Michael Woods, Post-Gazette National Bureau

WASHINGTON -- Government scientists yesterday wrote a new chapter in the book on how toxic environmental agents cause the genetic mutations behind cancer, birth defects and other ills.

"We have shown that environmental factors may cause cancer through a new pathway," said Dr. Dmitry A. Gordenin, of the National Institute of Environmental Health Sciences, part of the National Institutes of Health. It's a stealth approach, in which toxic agents target the "spell-checking/proofreading" mechanism that normally catches errors DNA makes naturally when copying itself.

Scientists have known that toxic chemicals, large doses of radiation, too much sunlight and other environmental factors can damage the double-helix molecule of heredity. Damage to the instructions for regulating a cell's growth, for instance, may allow the cell to divide wildly and turn cancerous. Damage to cells involved in reproduction may cause birth defects.

Gordenin and his associates used laboratory cell culture experiments to show that environmental agents also can cause such mutations indirectly, by disrupting the DNA system that repairs naturally occurring errors. Their research was published in the journal, Nature Genetics.

Called "mismatch repair," the system works like a computer spell checker. It swings into action when cells in the body divide to replace dying cells or grow new tissue. DNA duplicates as well. But the process is sloppy, and the instructions in fresh DNA are riddled with misspelled words.

The repair system dispatches special enzymes that patrol and spell check each new DNA strand, correcting the errors.

"Without the corrections, mutations would multiply and accumulate with each cell division," Gordenin explained in an interview. "That could lead to cancer, reproductive problems, birth defects and other problems."

In their experiments, the scientists showed that cadmium, a known human carcinogen, causes a 2,000-fold increase in mutations by blocking DNA repair.

"Genetically, this can result in a vast increase in errors that could be catastrophic," said Dr. Michael A. Resnick, a member of the research group.

Dr. Thomas A. Kunkel, another researcher, said mutations occurred with "remarkably small" amounts of cadmium, similar to real-world exposures that may occur in cadmium-related industry workers and smokers.

Cadmium is used in metal coatings, plastics, and so-called NiCad rechargeable batteries, and workers in those industries may be exposed. Until a 1997 ban, it was used as a fungicide for golf courses and home lawns.

Noting that cadmium remains in the environment for long periods, Gordenin said nobody knows how many people are still exposed from lawns and golf courses.

Cadmium is present naturally in small amounts in soil. Tobacco plants take cadmium up from the soil and concentrate it, so that cigarette smokers get double the average daily intake.

Michael Woods can be reached at mwoods@nationalpress.com or 1-202-662-7072.

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