Scientists Finger A Molecular Kingpin In Body's Response To ...( Using genetically modified knoc...)

Using genetically modified "knock-out" mice, scientists at the University of Rochester have produced the strongest evidence yet implicating a specific gene -- the same one that makes us susceptible to the pollutant dioxin -- as a vital link in the chemical cascade whereby cigarette smoke causes cancer. The finding comes thanks to a batch of genetically engineered mice normal in every way except for the deletion of the gene for the aromatic hydrocarbon, or AH, receptor; these mice had no damage from the same levels of cigarette smoke that caused significant gene damage in their normal brethren.

The work, reported in the November issue of Carcinogenesis, clarifies how cigarette smoke has an impact on our molecular machinery and should help researchers in their efforts to prevent genetic damage from the biochemical assault posed by smoking.

The team at the University's Environmental Health Science Center cautions that researchers must perform longer-term, larger studies and check in additional ways for evidence of gene damage to understand precisely how cigarette smoke damages our DNA, including the AH receptor's role. However, "It's quite possible that the AH receptor is one of the body's master switches that governs those pathways that control much of the gene damage from cigarette smoke," says principal author Tom Gasiewicz, professor of environmental medicine.

With every breath of cigarette smoke, the body is confronted by more than 4,000 chemicals; animals like humans and mice break some down into harmless byproducts and turn others into more dangerous compounds that wreak havoc throughout the body, breaking up or binding to our DNA and turning on or off important genes. Cancer typically develops because of such damage to several genes. While scientists have long known that every puff of cigarette smoke causes a molecular melee that plays a role in one-third of all cases of cancer, sorting out the primary culprits has been difficul
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Contact: Tom Rickey
trickey@admin.rochester.edu
716-275-7954
University of Rochester
23-Nov-1998