DNA rides along as asbestos enters cells.

DNA rides along as asbestos enter cells

Scientists have long sought to understand how asbestos causes cancer. Now they have identified a molecular mechanism that may underlie the process. "Asbestos can carry DNA into cells. What we have provided is a potential mechanism of mutagenesis in cells," says Edward M. Johnson of the Mount Sinai School of Medicine in New York City.

Measurable concentrations of DNA normally are present in fluid surrounding cells. In the October PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (Vol.85, No.20), Johnson, Jill D. Appel, Thomas M. Fasy and their colleagues suggest asbestos can carry pieces of this "exogenous" DNA into a cell, where genes on the DNA segments are later expressed. The research team took a common commercial form of asbestos, called chrysotile or "white" asbestos, and observed the DNA interaction using an electron microscope. The researchers found that the positively charged chrysotile surface attracted the negatively charged DNA.

They then found that the DNA-bound asbestos pierced the cell membrane. To illustrate this, they incubated monkey cells with marker DNA that conferred resistance to an antibiotic called neomycin. Cells still alive after researchers added neomycin were those that had taken up the resistant DNA.

Once inside the cell, exogenous DNA might create havoc in any of a number of ways, explains Appel. One possibility is that the DNA disrupts or shuts off genes that control the cell's normal growth. Alternatively, the DNA may carry a cancer-causing gene that is activated inside the cell; activate a cancer-causing gene that has remained quiescent in the host cell; or trigger the cell's repair enzymes, which copy DNA but can make mistakes that lead to mutations.

Geneticist George Dubes, at the University of Nebraska in Omaha, says the work has "great theoretical significance." Dubes and his colleagues had shown that silicate minerals similar to asbestos can enhance the uptake of viral RNA into cells, which prompted the Mount Sinai group's study.

The new research may help explain why asbestos exposure greatly increases a smoker's risk of lung cancer, Appel says. Modern cancer theory says a number of "insults" are needed before cancer develops -- and asbestos exposure may tip the balance for some smokers. Genetics also plays a role in the development of the disease; some people resist cancer even though they are exposed to more than one carcinogen, Appel notes.

Appel says the findings also may guide the development of safe alternatives to asbestos. With the knowledge that chrysotile asbestos carries a net positive charge, researchers might look for insulating materials that do not bind DNA.

Asbestos was widely used for several decades after World War II to insulate and fireproof buildings. The material's heyday was cut short by reports linking it to cancer. A landmark study led by another Mount Sinai researcher, Irving Selikoff, showed during the 1960s that insulation workers who handled asbestos died of cancer at high rates.