Pictures show smoking's ill effects on DNA.

Pictures show smoking's ill effects on DNA 

Scientists generally agree that the first step in the initiation of most cancers is the creation of adducts -- DNA changes that occur when a carcinogen covalently binds to genetic material. A husband-wife research team, using a radioactive labeling technique they pioneered, has begun mapping those changes. In the DNA of cancer patients who smoke cigarettes, radiographs show an adduct pattern that intensifies with the amount and duration of smoking. Moreover, trces of this adduct pattern can persist in former smokers for at least 14 years.

DNA is a polymer -- a long chain molecule -- whose basic units consist of nucleotides. The labeling process developed by Kurt and Erika Randerath, of Baylor College of Medicine in Houston, cleaves DNA into its individual nucleotides, labels each with radioactive phosphorus-32, then uses chromatography -- which separates a mix of chemicals into its individual components -- to spatially segregate normal nucleotides from those that have been modified by bulky aromatic chemicals, such as benzo(a)-pyrene and aromatic amines. To count adducts, the researchers measure radioactive decay in the phosphorus-32 tags.

The Randeraths used DNA separated from healthy tissue excised near cancers during the surgery of 18 people and from three cadavers. While DNA from the lung and heart contained the highest adduct levels, even the bladder, kidney, aorta and liver of longtime smokers showed the same pattern of adducts, report the Randeraths and their co-workers in the March 1 JOURNAL OF THE NATIONAL CANCER INSTITUTE.

In cigarette-smoking cancer-surgery patients, tissue near tumors of the lung, larynx, esophagus and epiglottis typically contained about one adduct per 10 million normal DNA nucleotides. "This level indicates quite a bit of damage," Kurt Randerath says. "Comparable to what has caused cancer in animals," it suggests "these levels may well be carcinogenic [in humans]."

The team has also applied the technique to scout for adducts caused by occupational exposure to specific aromatic chemicals. Their unpublished data, he says, show discrete dark points in the radiographs, not the broad-band smears seen among smokers--reflecting smoke's more complex mix of adduct-forming chemicals. More puzzling, he notes, is the finding that discrete aromatic-induced adducts also showed up in foundry workers' white blood cells, while the adduct pattern induced by aromatics in cigarette smoke was not visible in smokers' blood cells.

Though the Randeraths' technique is still in its infancy, "it's by far the most sensitive DNA-adduct detection technique, and as such is very exciting," says Stephen Hecht, who studies cigarette smoking and cancer at the American Health Foundation in Valhalla, N.Y. Hecht suspects it will not only reveal new clues to cancer causation, but will also indicate a way "to measure DNA adducts in a person the way we now measure cholesterol. It could give an indication of cancer susceptibility."