DNA Damage Shows Way Alcohol May Cause Cancer

The effort to place strong cancer warning labels in California bars and liquor stores and on alcoholic beverages themselves may receive a boost from newly discovered evidence of a chemical pathway by which alcohol could cause cancer.

UC Berkeley researchers reported Friday in the prestigious Proceedings of the National Academy of Sciences that alcohol and acetaldehyde--the principal product formed from alcohol in mammalian cells--combine in test-tube experiments to chemically change deoxyribonucleic acid (DNA), which serves as a blueprint for all living organisms.

The altered DNA produced by the chemicals is similar to that produced by other chemicals known to cause cancer, say molecular biologists Heinz Fraenkel-Conrat and Bea Singer of UC Berkeley. The alterations in DNA occur at concentrations of alcohol and acetaldehyde that would be produced by only one or two drinks, they said, suggesting that cancer could be caused even by moderate consumption of alcohol.

And while the researchers are unable to say exactly how much drinking might cause cancer, Singer said in a telephone interview, “I am convinced alcohol is a carcinogen.”

In the past, the only evidence linking alcohol and cancer has come from epidemiological studies suggesting a higher incidence of tumors of the breast, liver, rectum and oral cavity in humans who consume moderate to large amounts of alcohol.

The beer, wine and liquor industry, in resisting labeling, has argued that the carcinogenicity of alcohol has never been demonstrated in animals and that no one has shown a biochemical mechanism by which it could cause cancer--despite years of effort to do so.

If the new results can be duplicated in mammalian cells and in laboratory animals, that argument would be punctured, experts said. Michelle Corash, a lawyer who represents the alcohol industry, emphasized that no one had ever been able to demonstrate that alcohol causes cancer in animals. “Every other chemical that causes cancer in humans also causes it in animals,” she said, “so we don’t think alcohol is a carcinogen.”

However, because of the similarity of the alcohol-damaged DNA to DNA altered by known carcinogens, the Berkeley researchers believe that similar results will be found in animals.

A scientific advisory panel created by Gov. George Deukmejian under the terms of Proposition 65 recommended unanimously in April that alcohol be placed on the list of chemicals known by the state to cause cancer.

“This certainly reinforces our decision,” said panel member Alice Whittemore of Stanford University.

Will Appear on List July 1

Alcohol will appear on the toxics list July 1, Health and Welfare Undersecretary Thomas E. Warriner said. “We have always followed the advice of the science panel,” he noted. The industry will then have 12 months to work out how it will provide warning.

The most likely scenario now, experts said, is that warning signs linking cancer to alcohol abuse will be placed on the doors of liquor stores and bars, on restaurant menus and so forth.

But because the new research suggests that genetic damage can occur at alcohol levels associated with moderate drinking, the warning could be strengthened by changing “alcohol abuse” in the warning to “alcohol use,” Warriner said.

Many proponents of Proposition 65 have also urged that warning labels be placed on individual beverage containers. The new discovery could strengthen the call for such labeling.

Fraenkel-Conrat and Singer, who are husband and wife, studied the interaction of alcohol and acetaldehyde with the individual chemicals, called nucleotides, that form DNA.

Work in Combination

Neither alcohol nor acetaldehyde alone produced any change in the DNA. But when both were present, they combined with the nucleotides to form stable compounds called “mixed acetals.”

Similar compounds have been observed in the past from the reaction of other carcinogens with nucleotides. The reaction changes the shape of the individual molecules in DNA and thus impairs the cell’s ability to decode the genetic information contained in the DNA.

The impaired decoding may, for example, inhibit the production of proteins that restrain cellular proliferation, and thus lead to tumor formation.

Fraenkel-Conrat and Singer are working with biologist Martha R. Stampfer of the Lawrence Berkeley Laboratory to determine if alcohol and acetaldehyde can cause tumors in human breast cells grown in the laboratory. If tumors are formed there, the scientists will then go on to animal studies.