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ACS News Service Weekly PressPac: Wed Oct 25 16:42:03 EDT 2006

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News Items in this Edition

New evidence on why alcohol consumption is a risk factor for cancer

Why is alcohol consumption a risk factor for cancers of the oral cavity, pharynx, larynx, and esophagus? Scientists long have suspected that the culprit is acetaldehyde, a compound produced as the body breaks down the alcohol in beer, wine and hard liquor.

Now researchers in Japan have discovered direct molecular evidence supporting that link between acetaldehyde and alcohol-related cancers. In a report published in the current (October) issue of the monthly ACS journal Chemical Research in Toxicology, Tomonari Matsuda and colleagues studied DNA from the blood of 44 patients being treated for alcoholism.

They found that those patients with a variation in the aldehyde dehydrogenase gene also had increased amounts of the kind of DNA damage that can lead to cancer. The gene produces an enzyme that breaks down acetaldehyde. Individuals with the gene variant produce little aldehyde dehydrogenase and high levels of acetaldehyde build up in their blood after alcohol consumption.

Millions of people have the gene variant, which occurs mainly in individuals of East Asian heritage. “Taken together, the observations from biochemical, epidemiological, and molecular studies, in conjunction with this study, well fit the scenario that acetaldehyde is a primary causative factor in alcohol-induced cancers,” the scientists report.

Shedding light on the darkening of ancient Pompeii's paintings

Artists in ancient Pompeii painted the town red 2,000 years ago with a brilliant crimson pigment that dominated many of the doomed city's wall paintings. Now scientists in Europe report why those paintings are undergoing a mysterious darkening.

Marine Cotte and co-authors studied samples of those unique red pigments from wall paintings in a house near Pompeii that was buried under ash during the infamous eruption of Mount Vesuvius in 79 A. D. The paint, which used pigment made from red mercuric sulfide (called Cinnabar, HgS), was preserved under ash until excavations began in 1988. Since the 1990s, however, the brilliant red paintings have darkened and deteriorated.

In a report scheduled for the Nov. 1 issue of the ACS semi-monthly journal Analytical Chemistry, the authors describe how they used micro x-ray fluorescence and x-ray absorption spectroscopy at the European Synchrotron Radiation Facility to determine how the darkening could happen. The findings will help curators and restorers to develop better methods for preserving the brilliant artwork from ancient Rome, the report states.

Barbiturates are detectable in the environment 30 years after use peaked

Valium and other modern tranquilizers largely replaced barbiturate drugs 30 years ago. However, barbiturates are still detectable among the pharmaceutical and personal care products that wind up in the environment, researchers in Germany report.

Thomas P. Knepper and colleagues conducted what they believe to be the first systematic search for barbiturates in the environment. The results are scheduled for publication in the Dec. 1 issue of the ACS semi-monthly journal, Environmental Science & Technology. Use of phenobarbital and other barbiturates, once a mainstay of sedatives and hypnotics, has declined dramatically since introduction of safer alternatives in the 1970s.

Researchers knew that barbiturates have a chemical trait that makes compounds resistant to biodegradation; so they expected to find traces of barbiturates in groundwater sites that had been infiltrated by wastewater decades ago. Knepper's group was surprised, however, to find significant concentrations of the drugs in a river.

The river was near a landfill in Germany, and researchers suspect that barbiturates leaked out. They recommend monitoring ground water near landfills for barbiturates, especially those containing old medical waste. About 2,000 tons of barbiturates were produced each year in the United States during the 1960s, the study notes.

A potential anti-prion drug with “unprecedented” potency

The urgent search for a medication to treat prion diseases has led scientists in Germany to synthesize a new group of compounds, including one that is 15 times more potent than an approved drug now being tested in clinical trials. Their report is scheduled for the Nov. 2 issue of the biweekly ACS Journal of Medicinal Chemistry.

Prions are infectious proteins that cause brain disorders like Mad Cow Disease and Creutzfeldt-Jakob Disease (CJD) in humans. Peter Gmeiner and colleagues note that the recent emergence of a new form of CDJ, linked to consumption of infected beef mainly in Great Britain, intensified the search for anti-prion compounds. Most potential drugs have proved ineffective, often because they could not enter brain tissue where prions reside. One promising drug, however, is in clinical trials. That drug is quinacrine, already approved for several other medical conditions.

Gmeiner’s group describes the chemical synthesis and early laboratory testing of a family of anti-prion compounds that cross into brain tissue and combat prions. One of those compounds has what the report describes as “unprecedented” anti-prion activity, with 15 times greater potency than quinacrine.

Biotechs expand into small molecules for drug discovery

Biotech companies traditionally focus on large proteins in their quest to find new drugs. But faced with the complex nature of disease, these companies are increasingly turning to small molecules as well. This new push into small-molecule drug design, which researchers hope will deliver better and more effective disease treatments, is explored in a report scheduled for the Oct. 30 issue of Chemical & Engineering News, the ACS’s weekly newsmagazine.

Associate Editor Lisa M. Jarvis describes how major biotech companies such as Genentech and Amgen have moved into the small-molecule arena and expanded their chemistry operations in the process, including new partnerships with drug discovery firms. These efforts have increasingly brought together chemists from a wide range of disciplines, including medicinal, computational and process chemistry, Jarvis writes.

Biotech’s investment in small-molecule research is starting to pay off in the form of new drugs, she notes. A few companies already have commercialized new small-molecule drugs for the treatment of lung cancer and kidney disease, while drugs for multiple sclerosis, Parkinson’s and other diseases are making their way through the pipeline. By combining small-molecule approaches with protein research, biotech companies are boosting their odds of producing more effective treatments for some of our most challenging diseases, according to the article.

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