Carcinogen in cigarettes causes mutation linked to lung cancer

l. Then they observed the effects of the chemical using their mapping technique. They found that the carcinogen preferentially bound to the K-RAS gene at a mutational hot-spot called codon 12, an area especially vulnerable to mutation. Moreover, the researchers found that this site was not able to repair itself very well. The chemical did not bind significantly to other members of the RAS gene family.

Genes comprise codons, sequences of three chemicals that spell out the code for amino acids, the building blocks of proteins. The mapping technique relies in part on special enzymes that cut DNA where it has been damaged by the binding of a carcinogen, which is technically called a DNA adduct. Adducts cause mutations in codons.

Dr. Tang says that the study's findings provide further proof that smoking does cause lung cancer because the carcinogen bound most strongly to the precise site in the K-RAS gene that is frequently mutated in lung cancer. Using the same mapping technique, he says it may be possible to discover the environmental agent or agents that are causing the gene to mutate in pancreatic cancer, which is far more commonly associated with a codon 12 mutation than is lung cancer.

"If we could identify the agents that are causing the mutations, then we might be able to design effective measures to prevent this type of cancer," says Dr. Tang.

In the future, Dr. Tang hopes to identify the mechanisms that make the codon in the K-RAS gene more susceptible to damage. He also plans to explore the possibility that there may be individual differences in susceptibility to damage at this site, meaning that some people may be more prone to certain types of cancer.

In an editorial accompanying the study in the same issue of the Journal of the National Cancer Institute, researchers Michael J. Kelley and Susan J. Littman of Duke University Medical Center, Durham, NC, write: "[U]nderstanding the bio

Contact: Pam McDonnell
New York University Medical Center and School of Medicine

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