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Sickening DNA with Sunburns

Alaska's summer weather at its sunny best delights most of us, but it is a cause of distress for oncologists. Those cancer specialists know that exposure to sunlight, most especially its ultraviolet component, seems closely correlated to the occurrence of skin cancer. Yet "Stay out of the sun" ranks right up there with "Eat lots of broccoli" on the popular-advice list. Gimme chocolate, gimme sunshine, and I'11 listen to you once I get sick---that's the way most of us heed our doctors' well-meant wisdom.

Research has connected sunshine and skin cancer, but it's growing clearer that the true link lies in the genes---or at least in the genetic material, deoxyribonucleic acid or DNA for short.

Scientists working at the Johns Hopkins University in Maryland decided to test widely held views about DNA damage and cancer by using both human volunteers and test tubes. Their human volunteers were already in trouble. Some of them---88 people---had a type of skin cancer known as basal cell carcinoma. It sounds terrible, but as cancers go, it's comparatively easily treated and not a very dangerous ailment. The remaining 135 human guinea pigs had mild and noncancerous skin problems of different sorts. Participants ranged in age from 20 to 60 years, and all were Caucasian (that is, relatively unprotected by skin-darkening melanin pigment).

The Johns Hopkins researchers wanted to find out how well their experimental subjects could mend broken genes. They interviewed the participants about aspects of their medical history, paying special attention to family patterns of cancer and to episodes of sunburn. They had dermatologists evaluate the volunteers' skin conditions. And they took blood samples.

The sampled blood had work to do. In effect, the researchers turned each white blood cell into an experimental animal. They injected a bit of genetic material---a broken off chunk of gene---into the extracted cells.

The inserted DNA contains a code directing the cell to make a particular enzyme. It's an enzyme that natural human white blood cells never make. The enzyme is produced by a mutant bacteria, and that's where the code came from. But the human cells don't recognize the impostor; if they're healthy, with strong gene-mending abilities, they'll sweep the errant bits right in and incorporate them into the cellular machinery. Once in place, the code-containing DNA directs the white blood cells to crank out the unusual enzyme. The Johns Hopkins team incubated the cells, giving them 40 hours to fix the phony DNA damage, then measured the enzyme activity. That gave a very clear, quantifiable signal of how well the cells could fix damaged genes.

From the measurements, they found that adults lose nearly one percent of their natural ability to mend genetic damage with each year that passes. The older you are, then, the less able your system is to fix the cell errors that lead to cancer. They also found that young people with skin cancer had the repair capacity of people 30 years older. The younger victims of skin cancer also were more likely to have relatives who also had the disease, one more indication of a genetically linked susceptibility.

Overall, people with low DNA repair capacity were five times more likely to develop the cancer after intense sun exposure than were people with high repair capacity who shunned the sun. Women were more susceptible than men, especially if they had experienced six or more severe sunburns. Older women, those past menopause, retained 25 to 30 percent more repair capacity for their age if they were receiving estrogen-replacement therapy.

Perhaps someday the Johns Hopkins work will lead to a simple blood test establishing one's CSQ---cancer susceptibility quotient. Meanwhile, since we can't pick our ancestors, it seems the best thing we can do to avoid getting skin cancer is to avoid sunburning.